In utero teratogen exposure and cardiometabolic risk in 5-year-old children: a prospective pediatric study.

BACKGROUND: Aorta and carotid intima-media thickness (IMT) is a measure of subclinical atherosclerosis and useful to assess cardiometabolic risk in the young. The in utero milieu may involve cardiometabolic programing and the development of cardiometabolic risk factors in children. Maternal smoking, alcohol consumption, and micronutrient deficiencies during pregnancy influence the development of the cardiovascular system through a process of DNA methylation. AIM: To explore an association between maternal smoking and alcohol consumption during pregnancy and intima media thickness in 5-year-old children for a low-income setting. METHODS: Data were collected from 500 mother-child pairs at antenatal clinic visit, at birth, and at age 5 years. Anthropometric measurements were collected at birth and again at age 5 years. As well as clinical and ultrasound measurements at age 5 years. Clinical measurements, at age 5 years, included blood pressure, mean arterial pressure, and heart rate. Ultrasound measurements of the aorta and carotid arteries IMT were performed at age 5 years. Main outcome of interest was effect of dual teratogen exposure on the ultrasound measures IMT as indication of cardiometabolic risk. RESULTS: cIMT was significantly higher in children exposed to both alcohol and nicotine during pregnancy compared to those not exposed (p = .008). In separate linear models, dual in utero exposure (beta = 0.12; p = .01) and male sex (beta = 0.14; p = .01) were associated with higher right cIMT values (F(6,445) = 5.20; R2 = 0.07, p < .01); male sex (beta = 0.13; p = .01) and low birth weight (beta = 0.07; p = .01) with higher left cIMT value (F(4,491) = 4.49; R2 = 0.04; p = .01); and males sex (beta = 0.11; p = .02) with higher aorta IMT (F(6,459) = 5.63; R2 = 0.07; p < .01). Significant positive correlations between maternal measures of adiposity, maternal MUAC (r = 0.10; p = .03), and maternal BMI (r = 0.12; p < .01) and right cIMT measurements adjusted for the BMI of the child at age 5 years as covariate. Blood pressure measurements at age 5 years were not significantly associated with IMT but, instead, correlated significantly and positively with the BMI of the child at age 5 years (p < .01). CONCLUSION: Children exposed to both maternal smoking and alcohol consumption during pregnancy presented with cardiometabolic risk factors 5 years after birth. In addition, maternal adiposity, male sex, and low birth weight were associated with higher IMT at age 5 years.

The effects of in utero exposure to teratogens on organ size: a prospective paediatric study.

In low-income countries, prospective data on combined effects of in utero teratogen exposure are lacking and necessitates new research. The aim of the present study was to explore the effect of in utero teratogen exposure on the size of the kidneys and pancreas 5 years after birth in a low-income paediatric population. Data was collected from 500 mother-child pairs from a low-income setting. Anthropometric measurements included body weight, (BW) body height, mid-upper arm and waist circumference (WC). Clinical measurements included blood pressure (BP), mean arterial pressure and heart rate. Ultrasound measurements included pancreas, and kidney measurements at age 5 years. The main outcome of interest was the effect of maternal smoking and alcohol consumption on ultrasound measurements of organ size at age 5 years. Left and right kidney length measurements were significantly lower in smoking exposed children compared to controls (p = 0.04 and p = 0.03). Pancreas body measurements were significantly lower in smoking exposed children (p = 0.04). Multiple regression analyses were used to examine the associations between the independent variables (IDVs), maternal age, body mass index (BMI), mid-upper arm circumference (MUAC) and BW of the child, on the dependent variables (DVs) kidney lengths and kidney volumes. Also, the association between in utero exposure to alcohol and nicotine and pancreas size. WC was strongest (r = 0.28; p < 0.01) associated with pancreas head [F (4, 454) = 13.44; R2 = 0.11; p < 0.01] and tail (r = 0.30; p < 0.01) measurements at age 5 years, with in utero exposure, sex of the child and BMI as covariates. Kidney length and pancreas body measurements are affected by in utero exposure to nicotine at age 5 years and might contribute to cardiometabolic risk in later life. Also, findings from this study report on ultrasound reference values for kidney and pancreas measurements of children at age 5 years from a low-income setting.

Observation of persistent species temperature separation in inertial confinement fusion mixtures.

The injection and mixing of contaminant mass into the fuel in inertial confinement fusion (ICF) implosions is a primary factor preventing ignition. ICF experiments have recently achieved an alpha-heating regime, in which fusion self-heating is the dominant source of yield, by reducing the susceptibility of implosions to instabilities that inject this mass. We report the results of unique separated reactants implosion experiments studying pre-mixed contaminant as well as detailed high-resolution three-dimensional simulations that are in good agreement with experiments. At conditions relevant to mixing regions in high-yield implosions, we observe persistent chunks of contaminant that do not achieve thermal equilibrium with the fuel throughout the burn phase. The assumption of thermal equilibrium is made in nearly all computational ICF modeling and methods used to infer levels of contaminant from experiments. We estimate that these methods may underestimate the amount of contaminant by a factor of two or more.

Diagnostic accuracy of the ADOS and ADOS-2 in clinical practice.

The Autism Diagnostic Observation Schedule is a semi-structured, standardized assessment tool for individuals with suspected autism spectrum disorders (ASD) and is deemed to be part of the gold standard for diagnostic evaluation. Good diagnostic accuracy and interpersonal objectivity have been demonstrated for the ADOS in research setting. The question arises whether this is also true for daily clinical practice and whether diagnostic accuracy depends on specialized experience in the diagnostic evaluation. The present study explores the diagnostic accuracy of the original and the revised version of the ADOS for Modules 1 through 4. Thus, seven cases of ADOS executions were recorded and coded by a group of experts of specialized outpatient clinics for ASD. In an extensive consensus process, including video analysis of every minute of the ADOS executions, a "gold standard" coding for every case was defined. The videos of the ADOS administration were presented to a large group of clinicians (from daily clinical routine care) and their codings (n = 189) were obtained and analysed. Variance of coding and congruence with the expert coding were determined. High variance was found in the codings. The accuracy of the coding depends on the experience of the coder with the ADOS as well as on characteristics of the cases and the quality of the administration of the ADOS. Specialization in the diagnostic of ASD has to be claimed. Specialized outpatient clinics for ASD are required which guarantee a qualified diagnostic/differential diagnostic and case management with the aim of demand-oriented supply of individual cases.

Incidence of cancer and overall risk of mortality in individuals treated with raltegravir-based and non-raltegravir-based combination antiretroviral therapy regimens.

OBJECTIVES: There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. METHODS: The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. RESULTS: The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95-1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37-2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84-1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90-1.61) and 0.83 (95% CI 0.70-0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47-1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65-1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53-1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76-1.72 for RALvs. CONC). CONCLUSIONS: We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups.

Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood with substantial heritability. Pharmacological and molecular genetic studies as well as characterization of animal models have implicated serotonergic dysfunction in the pathophysiology of ADHD. Here, we investigated the effect of polymorphic variants in the gene of the tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme of serotonin (5-HT) synthesis in the brain, in children and adolescents with ADHD. We analyzed three single nucleotide polymorphisms (SNPs) in and downstream of the transcriptional control region of the TPH2 gene in 103 families with 225 affected children. Allelic association in families with more than one affected child was assessed using the pedigree disequilibrium test. Preferential transmissions were detected for the two SNPs in TPH2's regulatory region (rs4570625, P=0.049; rs11178997, P=0.034), but not for the third SNP in intron 2 (rs4565946, P=0.3517). Haplotype analysis revealed a strong trend of association between the regulatory region SNPs (rs4570625, rs11178997) and ADHD (P=0.064). Our results link potentially functional TPH2 variations to the pathophysiology of ADHD, and further support the relevance of 5-HT in disorders related to altered motor activity and cognitive processes.

Mutation screen of the brain derived neurotrophic factor gene (BDNF): identification of several genetic variants and association studies in patients with obesity, eating disorders, and attention-deficit/hyperactivity disorder.

Several lines of evidence indicate an involvement of brain derived neurotrophic factor (BDNF) in body weight regulation and activity: heterozygous Bdnf knockout mice (Bdnf(+/-)) are hyperphagic, obese, and hyperactive; furthermore, central infusion of BDNF leads to severe, dose-dependent appetite suppression and weight loss in rats. We searched for the role of BDNF variants in obesity, eating disorders, and attention-deficit/hyperactivity disorder (ADHD). A mutation screen (SSCP and DHPLC) of the translated region of BDNF in 183 extremely obese children and adolescents and 187 underweight students was performed. Additionally, we genotyped two common polymorphisms (rs6265: p.V66M; c.-46C > T) in 118 patients with anorexia nervosa, 80 patients with bulimia nervosa, 88 patients with ADHD, and 96 normal weight controls. Three rare variants (c.5C > T: p.T2I; c.273G > A; c.*137A > G) and the known polymorphism (p.V66M) were identified. A role of the I2 allele in the etiology of obesity cannot be excluded. We found no association between p.V66M or the additionally genotyped variant c.-46C > T and obesity, ADHD or eating disorders. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.

Molecular genetic aspects of attention-deficit/hyperactivity disorder.

Two genome wide scans, one of which was subsequently extended, have led to the identification of different chromosomal regions assumed to harbour genes underlying attention-deficit/hyperactivity disorder (ADHD). Some of these regions were also identified in patients with autism and/or dyslexia. The only region for which both studies detected a LOD score >1 was on chr 5p13 which is in the vicinity of the location of the candidate gene DAT1. The candidate gene approach has revealed the most robust and replicated findings for DRD4, DRD5, and DAT1 polymorphisms. Meanwhile interesting endophenotype studies have also been conducted suggesting a genetic basis for different diagnostic and therapeutic criteria. Animal studies for ADHD have investigated especially hyperactivity and have focused mainly on knockout and QTL designs. In knockout mice models the most promising results were obtained for genes of the dopaminergic pathway. QTL results in rodents suggest multiple loci underlying different forms of natural and induced hyperactivity. The molecular results mentioned above are presented and discussed in detail, thus providing both clinicians and geneticists with an overview of the current research status of this important child and adolescent psychiatric disorder.

Objective measurement of hyperactivity, impulsivity, and inattention in children with hyperkinetic disorders before and after treatment with methylphenidate.

PURPOSE: The purpose of this study was to investigate whether values of the respective parameters of the OPTAx test dependently differ due to the medication with methylphenidate (MPH) in children with hyperkinetic disorders (HD) suffering from hyperactivity, impulsivity, and attention deficits. METHODS: The OPTAx test is an infrared motion analysis to record the movement pattern during a continuous performance test. We tested 25 children between 6 and 12 years with HD (ICD-10: F90.0 or F90.1) before and after treatment with MPH. The parameters under investigation were activity (microevents and spatial scaling), impulsivity (errors of commission), and attentiveness (accuracy and variability). For statistical analysis a one-tailed matched pairs test (adj. p = 0.01) was conducted to discriminate differences found from those occurred at random. A post hoc partial correlation of absolute differences in the respective parameters and the daily dose of MPH (adj. for BMI) was performed if p < 0.01. RESULTS: Statistically significant results were found for microevents, spatial scaling, errors of commission, accuracy, and variability. The partial correlation showed significant results for microevents and variability. CONCLUSION: The mean pre-post changes found in all parameters investigated consistently correspond with benefits desired from medication with MPH in children with HD. Absolute differences in microevents and variability seem to depend on the daily dose of MPH after adjustment for BMI.

[Formal genetic findings in attention-deficit/hyperactivity-disorder]. / Formalgenetische Befunde zur Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung.

Twin, family and adoption studies have led to a solid understanding of the contribution of both genetic and environmental factors to the development of attention deficit/hyperactivity disorder (ADHD). We review recent studies under consideration of both methodological aspects and relevant findings. Heritability estimates in the range of 0.6 - 0.8 surpass those for most other child and adolescent psychiatric disorders. First degree relatives have elevated rates for ADHD, affective disorders, conduct disorders and substance abuse and dependency. The ADHD subtype of the index patient does not predict the subtype of other family members affected with ADHD; hence non-genetic factors seemingly account for this intrafamilial variability. Because the familial rates for ADHD are not higher in families of female in comparison to male index patients, there is no indication that the genetic loading is higher in affected females. Recently, rater effects have been discussed broadly: Whereas the heritability estimates are uniformly high independent of the informant (mother, father, teacher), the correlations between quantitatively rated symptoms are low between different informants. Knowledge of the formal genetic aspects of ADHD is a prerequisite for understanding the results of recent molecular genetic studies.

A decision tree for the early diagnosis of acute myocardial infarction in nontraumatic chest pain patients at hospital admission.

STUDY OBJECTIVE: To find an accurate algorithm for the diagnosis of acute myocardial infarction in nontraumatic chest pain patients on presentation to the emergency department. DESIGN: In a prospective clinical study, we compared the diagnostic performances of clinical symptoms, presenting ECG, creatinine kinase, creatine kinase MB activity and mass concentration, myoglobin, and cardiac troponin T test results of hospital admission blood samples. By classification and regression trees, a decision tree for the diagnosis of acute myocardial infarction was developed. SETTING: Emergency room of a Department of Internal Medicine (University Hospital). PATIENTS: One hundred fourteen nontraumatic chest pain patients (median delay from onset of chest pain to hospital admission, 3 h; range, 0.33 to 22): 26 Q-wave and 19 non-Q-wave myocardial infarctions, 49 patients with unstable angina pectoris, and 20 patients with chest pain caused by other diseases. MEASUREMENTS AND RESULTS: Of each parameter taken by itself, the ECG was tendentiously most informative (areas under receiver operating characteristic plots: 0.87 +/- 0.04 [ECG], 0.80 +/- 0.08 [myoglobin], 0.80 +/- 0.04 [creatine kinase MB mass], 0.77 +/- 0.04 [creatine kinase activity], 0.69 +/- 0.06 [clinical symptoms] 0.67 +/- 0.06 [creatine kinase MB activity], 0.67 +/- 0.05 [troponin T]). In patients presenting 3 h or less after the onset of chest pain, ECG signs of acute transmural myocardial ischemia were the best discriminator between patients with and without myocardial infarction. In patients presenting more than 3 h, however, creatine kinase MB mass concentrations (discriminator value, 6.7 micrograms/L) were superior to the ECG, clinical symptoms, and all other biochemical markers tested. This algorithm for diagnosing acute myocardial infarction was superior to each parameter by itself and was characterized by 0.91 sensitivity, a 0.90 specificity, a 0.90 positive and negative predictive value, and a 0.90 efficiency. CONCLUSIONS: We found an algorithm that could accurately separate the myocardial infarction patients from the others on admission to the emergency department. Therefore, this classifier could be a valuable diagnostic aid for rapid confirmation of a suspected myocardial infarction.

Rapid accurate diagnosis of acute myocardial infarction in patients with non-traumatic chest pain within 1 h of admission.

BACKGROUND: Accurate diagnosis of impending acute myocardial infarction (AMI) in patients presenting at an emergency department with acute chest pain is essential for proper triage and treatment. We have developed an algorithm for the early diagnosis of AMI. METHODS: The diagnostic performances of ECG, creatine kinase (CK) and creatine kinase isoenzyme MB (CKMB) activities, CKMB mass, myoglobin, and cardiac troponin T (cTnT) were compared for early diagnosis of AMI in 60 non-traumatic chest pain patients (22 AMI, 29 unstable angina, nine other diseases) on presentation to an internal medicine emergency department and 1 h thereafter. The classification and regression trees method was used for data analysis and revealed the following results. RESULTS: In patients with electrocardographic signs of acute transmural myocardial ischaemia on admission (mostly regional ST-segment elevations), biochemical markers could not improve the diagnostic accuracy either on admission or 1 h later. By contrast, in patients with non-diagnostic ECG, CKMB mass concentration measured 1h after admission was the best discriminator between AMI and non-AMI patients (discriminator value 5.8 micrograms/l) and was superior to ECG and all other biochemical markers tested. This algorithm for diagnosing AMI is characterized by 96% sensitivity, 90% specificity, 84% positive predictive value, 97% negative predictive value, 92% accuracy, 0.05 negative likelihood ratio, and 9.1 positive likelihood ratio. CONCLUSION: The classification procedure obtained allows accurate rapid and early diagnosis of AMI and could therefore be a valuable diagnostic aid to physicians of emergency medicine.

Dissolution kinetics of griseofulvin in mixed micellar solutions.

The dissolution kinetics of the poorly water soluble, lipophilic model drug substance griseofulvin were studied in solutions containing simple and mixed micelles of sodium cholate (BS) and phosphatidylcholine (PC). Variables under investigation were the concentration of BS and the ratio PC/BS. A rotating disk apparatus was used to monitor the dissolution process. With this method, (mixed) micellar diffusion coefficients could be calculated and some detailed information about the physicochemical behavior and composition of mixed PC/BS micelles could be derived.

Early release of glycogen phosphorylase in patients with unstable angina and transient ST-T alterations.

OBJECTIVE: To determine whether transient ST-T alterations in patients with unstable angina are associated with an increase in plasma glycogen phosphorylase BB concentrations on admission to hospital. DESIGN: Prospective screening of patients with unstable angina for markers of myocardial cell damage. SETTING: Accident and emergency department of university hospital. PATIENTS: 48 consecutive patients admitted for angina pectoris (18 with transient ST-T alterations). None of the patients had acute myocardial infarction according to standard criteria. MAIN OUTCOME MEASURES: Creatine kinase and creatine kinase MB activities, creatine kinase MB mass concentration, and myoglobin, cardiac troponin T, and glycogen phosphorylase BB concentrations on admission. RESULTS: All variables except for creatine kinase and creatine kinase MB activities were significantly higher on admission in patients with unstable angina and transient ST-T alterations than in patients without. However, glycogen phosphorylase BB concentration was the only marker that was significantly (p = 0.0001) increased above its discriminator value in most patients (16). In the 18 patients with transient ST-T alterations creatine kinase MB mass concentration and troponin T and myoglobin concentrations were significantly (p = 0.0001) less commonly increased on admission (in five, three, and two patients, respectively). CONCLUSIONS: The early release of glycogen phosphorylase BB may help to identify high risk patients with unstable angina even on admission to an emergency department. Glycogen phosphorylase BB concentrations could help to guide decisions about patient management.

Early diagnosis of acute myocardial infarction by a newly developed rapid immunoturbidimetric assay for myoglobin.

OBJECTIVE: To evaluate a rapid immunoturbidimetric assay for myoglobin and to investigate its clinical usefulness in the early detection of acute myocardial infarction. DESIGN: Prospective study. Immunoturbidimetrically determined myoglobin concentrations were compared with radioimmunoassay results obtained with the same blood samples. The diagnostic performance of myoglobin determination was compared with creatine kinase and creatine kinase MB activity (current standard of routine diagnosis). SETTINGS: Part 1: coronary care unit. Part 2: emergency room in a university hospital. PATIENTS: Part 1:30 patients with acute myocardial infarction admitted not later than four hours (median two hours) after the onset of symptoms. Part 2: 126 patients admitted to the emergency room with chest pain not caused by trauma (51 cases of acute myocardial infarction, 51 cases of angina pectoris, and 24 cases of chest pain not related to coronary artery disease). INTERVENTIONS: Part 1: routine treatment including intravenous thrombolytic treatment (28 patients). Part 2: routine emergency treatment without thrombolytic treatment. MAIN OUTCOME MEASURES: The analytical quality of the immunoturbidimetric myoglobin assay and a comparison between the myoglobin assay and creatine kinase and creatine kinase MB for diagnostic sensitivity and performance. RESULTS: The immunoturbidimetric myoglobin assay was fast and convenient and gave myoglobin determinations of high analytical quality. The concentration of myoglobin increased, peaked, and returned to the reference range significantly earlier than creatine kinase (p < or = 0.0001) and creatine kinase MB (p < or = 0.0002). Before thrombolytic therapy was started the diagnostic sensitivity of myoglobin was significantly higher than that of creatine kinase MB activity 0-6 h after the onset of chest pain and significantly higher (0.82 v 0.29) than creatine kinase 2-4 h after the onset of chest pain. In almost all patients (92%) plasma myoglobin concentrations were increased 4-6 h after the onset of chest pain. CONCLUSION: Myoglobin was more sensitive in detecting early myocardial infarction than creatine kinase and creatine kinase MB activity. Immunoturbidimetric myoglobin measurements could be useful in the early evaluation of patients with suspected myocardial infarction because this assay takes less than two minutes.

Early detection of acute myocardial infarction by measurement of mass concentration of creatine kinase-MB.

The diagnostic sensitivity and performance of immunoenzymometric measurements of creatine kinase (CK)-MB mass concentrations in the early diagnosis of acute myocardial infarction (AMI) were examined and compared with the sensitivities and performances of CK and CK-MB activity, in the context of simultaneous measurements of CK, CK-MB activity, and CK-MB mass concentrations in serially drawn blood samples obtained immediately from 36 patients with AMI and 126 patients with chest pain on admission to the emergency room of the department of internal medicine. In the 36 patients with AMI, who were all admitted no later than 4 hours after the onset of chest pain, pathologic increase occurred significantly earlier in CK-MB mass than in both CK and CK-MB activity, with a median difference of 1 hour each. In patients coming to the emergency room (51 with AMI, 51 with angina pectoris and 24 with chest pain not related to coronary artery disease), CK-MB mass was the best diagnostic measurement for AMI of all markers tested (significantly higher efficiency, Youden index and likelihood ratio than both CK and CK-MB activity). Before initiating thrombolytic therapy, the sensitivity of CK-MB mass is significantly higher than CK-MB activity during the 0- to 6-hour period and significantly higher than CK activity during the 2- to 4-hour period after the onset of chest pain. Consequently, it is often possible to diagnose an AMI on the basis of increased CK-MB mass concentrations even at a time when CK and CK-MB activities are still within the reference interval.

Cardiac troponin T in diagnosis of acute myocardial infarction.

Troponin T is a structurally bound protein found in striated muscle cells. We tested concentrations of its cardiac-specific isotype in peripheral venous blood samples serially drawn from 72 patients with confirmed myocardial infarction. Fifty-nine patients received thrombolytic treatment with intravenous streptokinase, urokinase, or recombinant tissue-type plasminogen activator; because of contraindications, the remaining 13 patients did not. Concentrations of troponin T in plasma, measured by an enzyme-linked immunosorbent assay, started increasing within a few hours after the onset of symptoms (median, 4 h; range, 1-10 h). The sensitivity of troponin T for detecting myocardial infarction was 100% from 10 to 120 h after the onset of symptoms; sensitivity on the seventh day after admission was 84%. Concentrations were increased for up to three weeks in some patients with late or high peak values. Successful reperfusion in Q-wave infarction obviously influences the release of troponin T into plasma, with all such cases showing peak values less than or equal to 26 h (median, 14 h) after the onset of symptoms. Troponin T concentrations in these patients returned to within the reference interval more rapidly than in nonreperfused subjects. In the 13 patients without fibrinolytic therapy, troponin T tended to peak approximately 48 h (median) after the onset of chest pain. Troponin T concentrations in patients for whom thrombolysis was unsuccessful resembled those in patients without fibrinolytic therapy. The specificity of the assay was 96% as tested in samples of 96 emergency-room patients. The reference interval (less than 0.5 micrograms/L) was established from samples of 100 healthy blood donors. Troponin T measurements are a specific and sensitive method for the early and late diagnosis of acute myocardial infarction and could, therefore, provide a new criterion in laboratory diagnosis of its occurrence.

Dissolution rate of griseofulvin in bile salt solutions.

Bile salts increase the apparent solubility of lipophilic poorly water-soluble drugs like griseofulvin. In this study, the dissolution kinetics of griseofulvin in solutions of bile salts (sodium taurocholate and sodium cholate) were investigated. A rotating disk apparatus was chosen to monitor dissolution kinetics; it well-defined hydrodynamic conditions allowed for analysis of the behavior of bile salt micelles under different conditions. Griseofulvin solubility and dissolution rate increased with increasing bile salt concentration in the dissolution medium. The enhancement of the dissolution rate was not linearly related to the solubility increase, as diffusional transport of the solubilized drug proved to be less efficient than transport of the unsolubilized ("free") drug. The dissolution process proved to be controlled by convective diffusion. An analysis of the data with the phase separation model provided results for the micellar diffusion coefficient comparable with literature data obtained with different techniques.

Is the magnetic resonance imaging proton spin-lattice relaxation time a reliable noninvasive parameter of developing liver fibrosis?

During the development of liver fibrosis in rats by an individual dose-titrated CCl4 administration, hepatic proton spin-lattice relaxation time (T1) has been measured in vivo every 2 weeks for 8 weeks. Liver content of collagen, triglycerides and water has been measured biochemically in biopsy material. After 4 weeks of CCl4 treatment, T1 increased significantly and remained at the same level, whereas liver collagen reached its maximum at 8 weeks. It is concluded that, under our experimental conditions, increased hepatic T1 represents drug-induced edema and that hepatic T1 is not a reliable noninvasive parameter for developing liver fibrosis in vivo.