Severe intrahepatic cholestasis of pregnancy is a risk factor for preeclampsia in singleton and twin pregnancies.

OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is known to be associated with fetal complications. It recently was suggested to be associated possibly with preeclampsia (PET) as well. The objective of this study was to investigate that possibility. STUDY DESIGN: The study group included 78 women (54 singleton and 24 twin pregnancies) who had been diagnosed with ICP based on clinical presentation, elevated liver enzymes, and elevated total bile acids (>10 µmol/L). Disease severity was based on total bile acids levels as being severe (>40 µmol/L), moderate (20-40 µmol/L), or mild (10-20 µmol/L). The course of disease was reviewed carefully in each case. The control groups were comprised of apparently healthy women with singleton (n = 200) and twin (n = 100) pregnancies that were drawn randomly from a computerized registry of all the deliveries in our institution during the study period. RESULTS: The total incidence of PET was significantly higher for the patients with ICP who had singleton and twin pregnancies compared with the control groups (singletons: 7.4% vs 1.5%; P < .05; twins: 33.3% vs 6.2%; P < .05, respectively). The incidence of severe PET was also significantly higher in both singleton (11-fold) and twin (8-fold) pregnancies compared with control subjects. Severe ICP, but not mild ICP, was a major risk factor for PET among women with either singleton or twin pregnancies. The timing of the initial presentation of ICP had no effect on PET incidence rates. Preeclampsia occurred usually 2-4 weeks after the diagnosis of ICP, and proteinuria preceded elevated blood pressure in all cases. Moreover, the total bile acid levels among 33 women who were diagnosed as having PET, but not ICP, were within normal range. CONCLUSION: ICP increases the incidence of PET; severe disease was a major risk factor for preeclampsia. Therefore, we strongly suggest including routine evaluation for preeclampsia in the treatment of women with moderate and severe ICP.

The association of higher levels of within-normal-limits liver enzymes and the prevalence of the metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) is frequently characterized by elevated liver enzymes, including gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT). Our objective was to evaluate the range of prevalence of MetS in apparently healthy individuals whose liver enzyme concentrations were all within-normal-range. METHODS: We have performed a cross sectional analysis on participants of the Tel-Aviv medical center inflammation survey (TAMCIS) recruited between the years 2003-2009. Analyzed were a cohort of 6,561 men and 3,389 women. RESULTS: The prevalence of MetS increased significantly from the first quintile to the fifth for both GGT and ALT, all the five quintiles being in the normal range. Logistic regression analysis for the presence of MetS showed crude odds ratios of 2.7 and 2.4 between the first and fourth quintiles and 3.6 and 3.2 for the fifth quintile in men and women respectively for ALT. For GGT the respective odds being 3.6 and 3.2 for the fourth quintile and 3.9 and 3.4 for the fifth quintile in men and women, respectively. CONCLUSIONS: A relatively high prevalence of MetS was noted in a cohort of apparently healthy individuals with liver enzyme concentrations within-normal-limits. Practical consequences include the need to follow up these enzyme concentrations as continuous variables and to take into consideration that even relatively small elevations within the normal range might reflect the presence of dysmetabolism.

Platelet poor plasma serotonin level in delinquent adolescents diagnosed with conduct disorder.

OBJECTIVE: Accumulating data indicate the involvement of the serotonergic system in adolescent aggression. The aim of this study was to examine the platelet-poor plasma (PPP) serotonin (5-HT) levels among delinquent adolescent boys with conduct disorder (CD) in comparison with normal controls. METHOD: PPP 5-HT levels were measured in 16 male delinquent CD adolescents from a correctional facility and in 14 normal male adolescent controls. Severity of aggressive behavior was assessed by the Child Behavior Checklist (CBCL) and the Overt Aggression Scale (OAS). RESULTS: Delinquent CD adolescents had higher PPP 5-HT levels (about 3-fold) than the normal controls (27.68+/-32.29 vs. 7.76+/-4.23 ng/ml, respectively, p=0.027). In the delinquent CD adolescents a significant correlation was found between the PPP 5-HT levels and the CBCL and OAS aggressive scores (r=0.68, p=0.0034 and r=0.59, p=0.016, respectively). CONCLUSIONS: Juvenile delinquency is associated with high PPP 5-HT levels. Modulation of 5-HT neurotransmission may have a role in the symptomatology and treatment of severe adolescent CD.

Comparative analysis of Bayer wide-range C-reactive protein (wr-CRP) and the Dade-Behring high sensitivity C-reactive protein (hs-CRP) in patients with inflammatory bowel disease.

OBJECTIVE: The recently introduced Bayerwide-range C-reactive protein (wr-CRP) assay might be relevant for the real-time low-cost and online determination of inflammatory bowel disease (IBD) activity. Our aim was to examine whether wr-CRP can substitute for the Dade Behring high sensitivity C-reactive protein (hs-CRP) assay in IBD patients. METHODS: A total of 71 patients with IBD, of whom 48 had Crohn's disease CD and 23 had ulcerative colitis (UC) with various intensities of disease activity participated in the study. The CRP of patients who were under treatment at the Department of Gastroenterology and Liver Diseases were measured using both wr-CRP and the hs-CRP. RESULTS: A significant (r = 0.995; P < 0.001) correlation was noted between the hs-CRP and wr-CRP measurements for the whole sample as well as for the two diseases, CD (r = 0.994; P < 0.001) and UC (r = 0.997; P < 0.001), which were analyzed separately. CONCLUSION: The Bayer wr-CRP assay might be a useful low-cost and real-time inflammation-sensitive biomarker in patients with IBD.

Introducing the wide range C-reactive protein (wr-CRP) into clinical use for the detection of microinflammation.

BACKGROUND: The determination of low grade inflammation in apparently healthy individuals (microinflammation) has prognostic significance in terms of future vascular events and accelerated atherothrombotic disease. METHODS: We compared the Bayer wide range (wr)-C-reactive protein (CRP) immunoturbidometric assay on the ADVIA 1650 system to the Dade Behring high sensitivity (hs)-CRP on the BNII Nephelometer in 1446 apparently healthy individuals having a relatively low (<10 mg/l) concentration. The correlation between the 2 assays was also analyzed in relation to other commonly used microinflammatory biomarkers. RESULTS: A significant (p<0.0005) correlation was noted between the hs-CRP and the wr-CRP for the entire cohort (r=0.99) as well as for both women (r=0.99 n=483) and men (r=0.99 n=963). The mean difference between the measures (hs-CRP minus wr-CRP) was -0.039 (SD 0.317). The Deming regression results for the entire cohort showed a slope of 1.112+/-0.004 and an intercept of -0.263+/-0.01. CONCLUSIONS: The Bayer wr-CRP assay performed presents a reasonable alternative to the Behring Dade hs-CRP assay. The advantages of the wr-CRP assay are its online and real time availability as well as lower costs.

Low platelet-poor plasma levels of serotonin in adult autistic patients.

BACKGROUND: Hyperserotonemia has been reported in about a third of autistic patients. However, most studies have examined whole blood levels of serotonin (5-HT), the vast majority of which is found in platelets. The aim of this study was to determine 5-HT levels in platelet-poor plasma (PPP) in a group of adult patients with autism. METHODS: Levels of PPP 5-HT were compared between 10 adult drug-free autistic patients and 12 healthy controls. The Ritvo-Freeman Real-Life Rating Scale and the Overt Aggression Scale (OAS) were administered to the autistic group as a measure of symptom severity. RESULTS: Significantly lower PPP 5-HT levels were observed in the autistic group as compared to the controls (p = 0.03). In addition, PPP 5-HT levels were inversely correlated with OAS scores among subjects with autism (r = -0.64, p < 0.05). CONCLUSION: PPP 5-HT ('free') levels appear to be low in autistic patients and may play a role in the pathophysiology and symptomatology of the disorder.

Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: a randomized, placebo-controlled study.

BACKGROUND: The number of patients awaiting heart transplantation is increasing in proportion to the waiting period for a donor. Studies have shown that coenzyme Q10 (CoQ10) has a beneficial effect on patients with heart failure. HYPOTHESIS: The purpose of the present double-blind, placebo-controlled, randomized study was to assess the effect of CoQ10 on patients with end-stage heart failure and to determine if CoQ10 can improve the pharmacological bridge to heart transplantation. METHODS: A prospective double-blind design was used. Thirty-two patients with end-stage heart failure awaiting heart transplantation were randomly allocated to receive either 60 mg U/day of Ultrasome--CoQ10 (special preparation to increase intestinal absorption) or placebo for 3 months. All patients continued their regular medication regimen. Assessments included anamnesis with an extended questionnaire based partially on the Minnesota Living with Heart Failure Questionnaire, 6-min walk test, blood tests for atrial natriuretic factor (ANF) and tumor necrosis factor (TNF), and echocardiography. RESULTS: Twenty-seven patients completed the study. The study group showed significant improvement in the 6-min walk test and a decrease in dyspnea, New York Heart Association (NYHA) classification, nocturia, and fatigue. No significant changes were noted after 3 months of treatment in echocardiography parameters (dimensions and contractility of cardiac chambers) or ANF and TNF blood levels. CONCLUSIONS: The administration of CoQ10 to heart transplant candidates led to a significant improvement in functional status, clinical symptoms, and quality of life. However, there were no objective changes in echo measurements or ANF and TNF blood levels. Coenzyme Q10 may serve as an optional addition to the pharmacologic armamentarium of patients with end-stage heart failure. The apparent discrepancy between significant clinical improvement and unchanged cardiac status requires further investigation.

The platelet-poor plasma 5-HT response to carbohydrate rich meal administration in adult autistic patients compared with normal controls.

There are cumulative data indicating involvement of the 5-HT system in autistic disorder. Most studies examining 5-HT function have focused on whole blood 5-HT content. The carbohydrate-rich meal test (CRMT) is a dietary manipulation that could significantly influence platelet-poor plasma (PPP) 5-HT levels and reflect the responsiveness of the serotonergic system in 'free' plasma. In this study, CRMT was used as an indicator of 5-HT responsivity in drug-free adults with autistic disorder (n = 7), compared with normal controls (n = 10). The PPP 5-HT levels were measured at baseline and during 3 h after administration of the CRMT. A significant elevation in PPP 5-HT levels in adult autistic patients was reached 60 min after meal administration (p < 0.03 vs control and p = 0.05 vs baseline) and a significant decrease was noted after 120 min (p < 0.01 vs baseline). In contrast to the biphasic response of the autistic patients, normal controls exhibited a gradual linear increase of PPP 5-HT levels. Our results indicate that in adult autistic patients, the pattern of PPP 5-HT responsivity to a dietary challenge of CRMT is dysregulated compared with normal controls and provide further support for the role of 5-HT in autism.

Reduction in resting metabolic rate and ratio of plasma leptin to urinary nitric oxide: influence on obesity-related hypertension.

BACKGROUND: Multiple factors are involved in the pathogenesis of hypertension in the obese individual OBJECTIVE: To evaluate the role of a decrease in sympathetically mediated thermogenesis and the effect of the correlation between the plasma leptin and daily urinary nitric oxide levels on obesity-related hypertension. METHODS: We evaluated three groups: 25 obese hypertensive patients (age 45.7 +/- 1.37 years, body mass index 34.2 +/- 1.35 kg/m2, systolic/diastolic blood pressure 155 +/- 2.9/105 +/- 1.3, mean arterial pressure 122 +/- 1.50 mmHg); 21 obese normotensive patients (age 39.6 +/- 1.72, BMI 31.3 +/- 0.76, SBP/DBP 124 +/- 2.1/85.4 +/- 1.8, MAP 98.2 +/- 1.80); and 17 lean normotensive subjects (age 38.1 +/- 2.16, BMI 22.1 +/- 0.28, SBP/DBP 117 +/- 1.7/76.8 +/- 1.5, MAP 90.1 +/- 1.50). We determined basal resting metabolic rates, plasma insulin (radio-immunoassay), norepinephrine (high performance liquid chromatography) in all subjects. Thereafter, 14 obese hypertensives underwent a weight reduction diet. At weeks 6 (n = 14) and 14 (n = 10) of the diet the above determinations were repeated. Plasma leptin (enzyme-linked immunosorbent assay) and UNOx (spectrophotometry) were assayed in 17 obese hypertensives and 17 obese normotensives, and in 19 obese hypertensives versus 11 obese normotensives, respectively. RESULTS: Obese hypertensive patients had significantly higher basal RMR and plasma NE levels insulin levels were lower in the lean group, with no difference between the hypertensive and normotensive obese groups. At weeks 6 and 14, BMI was significantly lower, as were insulin and NE levels. RMR decreased to values of normotensive subjects. MAP normalized but remained significantly higher than in obese normotensives. Leptin blood levels and the leptin/UNOx ratio were significantly higher in the obese hypertensive compared to the obese normotensive patients. Both these parameters were strongly correlated to BMI, MAP, RMR, and plasma NE and insulin. Obese hypertensive patients excreted less urinary NO metabolites. A strong correlation was found between MAP and the leptin/UNOx ratio. CONCLUSIONS: A reduction in sympathetically mediated thermogenesis, as reflected by RMR, results in normalization of obesity-related hypertension. In contrast, insulin does not seem to play a major role in the pathogenesis of hypertension associated with obesity. Increased leptin levels in conjunction with decreased NO production in the presence of enhanced sympathetic activity may contribute to blood pressure elevation in the obese.

Plasma serotonin response to carbohydrate-rich food in chronic schizophrenic patients: clozapine versus classic antipsychotic agents.

Researchers have reported a stimulatory effect of carbohydrate-rich intake on platelet-poor plasma (PPP) serotonin (5-HT) levels in healthy human subjects. Dietary manipulation may serve as a safer and less invasive means than pharmacologic challenge to provoke serotonergic responsivity in studies of schizophrenia. In the present study, we used the carbohydrate-rich meal test as an indicator of 5-HT activity in 12 patients with chronic schizophrenia maintained for at least 6 months on clozapine. PPP 5-HT levels were measured at baseline and at 1, 2 and 3 h after administration of the test. Findings were compared with those in schizophrenic patients treated with classic antipsychotic agents for the same duration. The maximal PPP 5-HT response was reached 120 min after meal administration in the clozapine-treated group and 60 min after in the classic antipsychotic-treated group (P<0.05 vs baseline for both). The 5-HT level (as percentage of baseline) at 60 min was significantly lower in the clozapine-treated group (P<0.02), as were individual PPP 5-HT peak values (P<0.05). The individual time to reach the peak response was similar in the two groups. Our results indicate that in patients with chronic schizophrenia 5-HT responsivity to the natural challenge of carbohydrate-rich meals is lower in those treated with clozapine than in those given classic antipsychotic agents. Values in both groups were lower than those in an appropriate historical comparative group of healthy subjects. We suggest that both clozapine and classic antipsychotic agents suppress serotonergic system sensitivity, but to a different degree. Copyright 2001 John Wiley & Sons, Ltd.