Radioiodinated tracers for the evaluation of dopamine receptors in the neonatal rat brain after hypoxic-ischemic injury

In order to evaluate in vivo single-photon emission tomography (SPET) method of assessing cerebral function after hypoxic-ischemic injury in human neonates, we studied D₁ and D₂ dopamine receptors in a rat model. Seven-day-old rats underwent permanent unilateral common carotid ligation followed by exposure to 8% O₂. Two weeks later, in brains with no visible loss of hemispheric volume, striatal dopaminergic receptors were studied, with [¹²⁵I]TISCH and [1251]IBZM for the D₁ and D₂ dopamine receptors, respectively. Using [¹²⁵I]TISCH, we observed no modifications of D₁ receptors, but in contrast, ex vivo and in vitro autoradiographic experiments showed a 40% decrease in the striatal binding of [¹²⁵I]IBZM on both the ipsilateral and the contralateral side to the carotid ligation. These alterations were detected with IBZM, a D₂ dopamine receptor ligand usable for SPET imaging. Therefore, exploration of D₂ receptors by SPET in human neonates suffering from perinatal hypoxia-ischemia may be valuable for the diagnosis and follow-up of cerebral function damages. Correspondence to: D. Guilloteau     

In vitro metabolism of ferroquine (SSR97193) in animal and human hepatic models and antimalarial activity of major metabolites on Plasmodium falciparum.

Ferroquine (SSR97193) has been shown to be a promising antimalarial, both on laboratory clones and on field isolates. So far, no resistance was documented in Plasmodium falciparum. In the present work, the metabolic pathway of ferroquine, based on experiments using animal and human hepatic models, is proposed. Ferroquine is metabolized mainly via an oxidative pathway into the major metabolite mono-N-demethyl ferroquine and then into di-N,N-demethyl ferroquine. Some other minor metabolic pathways were also identified. Cytochrome P450 isoforms 2C9, 2C19, and 3A4 and, possibly in some patients, isoform 2D6, are mainly involved in ferroquine oxidation. The metabolites were synthesized and tested against the 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) P. falciparum strains. According to the results, the activity of the two main metabolites decreased compared with that of ferroquine; however, the activity of the mono-N-demethyl derivative is significantly higher than that of chloroquine on both strains, and the di-N-demethyl derivative remains more active than chloroquine on the chloroquine-resistant strain. These results further support the potential use of ferroquine against human malaria.     

Pharmacological approaches to reducing blood loss and transfusions in the surgical patient

Purpose

To review the efficacy, effectiveness and safety of hemostatic drugs to reduce surgical blood loss.

Methods

Analysis of randomized controlled trials and metaanalyses exploring the efficacy of desmopressin, aprotinin, lysine analogues and recombinant activated factor VII (rFVIIa) on clinically important endpoints.

Main findings

Although potentially useful in surgical patients with mild hemophilia or type I von Willebranďs disease, desmopressin has no proven benefit in patients without previous hemostatic defects. Aprotinin has been studied extensively in cardiopulmonary bypass surgery, with evidence of a blood sparing effect. Additional benefits are suggested. The drug is less consistently effective in liver transplantation and major orthopedic surgery. Although rare, hypersensitivity reactions to aprotinin may occur, especially on re-exposure. Tranexamic acid can reduce blood transfusion in cardiac surgery, liver transplantation and total knee arthroplasty surgery with a satisfactory safety profile. Epsilon aminocaproic acid has not been investigated adequately, despite its widespread use. While rFVIIa may be beneficial in controlling massive coagulopathic bleeding in trauma and surgical patients, there is currently no evidence to support its prophylactic use in elective surgical patients.

Conclusion

Aprotinin and tranexamic acid are valuable pharmacologic options for reducing surgical bleeding. The expected benefit of these drugs is highly dependent on the actual blood usage for a given procedure at the institutional level. More studies using clinically significant endpoints are necessary to assess the relative efficacy and optimal dosing of these drugs.

     

Dual activity maps in primate visual cortex produced by different temporal patterns of zif268 mRNA and protein expression

The inducible nature of the immediate-early genes (IEGs) c-fos and zif268 allows their products to be used as activity markers in the brain. The utility of such markers in general is restricted because they can resolve only neurons activated by a single stimulus. To overcome this limitation, we have developed a double-label technique that exploits the dissimilar time course of zif268 mRNA and protein induction, allowing them to be separately induced by two different stimuli and independently stained to provide a visual display of neurons that are responsive to each stimulus. Two powerful features of this new imaging technique—the possibility of staining separate populations of activated neurons and the ability to visualize them at the cellular level—should extend IEG applications in biological activity mapping.     

Contribution of glucose tolerance and plasma insulin levels to the relationships between body fat distribution and plasma lipoprotein levels in women.

Numerous interrelated metabolic and morphological variables such as plasma insulin levels, glucose tolerance and abdominal obesity are associated with changes in plasma lipoprotein levels. The present study was undertaken to differentiate, using a multivariate approach, the respective contributions of plasma glucose and insulin levels, obesity and regional adipose tissue distribution to the variance in plasma lipoproteins. The study group was composed of 69 healthy premenopausal women (age 35.4 +/- 5.0 years (mean +/- s.d.); percent body fat 40.7 +/- 10.1). Indices of carbohydrate metabolism showed significant univariate correlations with triglyceride (TG) and/or cholesterol (CHOL) content of plasma VLDL, LDL and HDL (P less than 0.05). Multivariate analyses indicated that the explained variance in plasma VLDL-TG (R2 x 100 = 44 percent, P less than 0.05) and LDL-apoprotein (apo) B levels (R2 x 100 = 33.1 percent, P less than 0.08) was entirely accounted for by indices of carbohydrate metabolism and body fat distribution, whereas total body fatness added no significant contribution to these models. Multivariate analyses also revealed that the best possible regression model to predict the variation in plasma HDL2-CHOL levels only included computed tomography-derived deep abdominal adipose tissue area (P less than 0.0001). All other variables were unable to further improve the explained variance in plasma HDL2-CHOL levels. In partial correlation analyses, indices of carbohydrate metabolism and the waist-to-hip circumference ratio (WHR) remained significantly correlated with plasma VLDL-TG and LDL-apo B levels after adjustment of VLDL-TG and LDL-apo B for either insulin and glucose levels, or for the WHR (P less than 0.08). After correcting for deep abdominal fat accumulation, no significant correlation was observed between indices of carbohydrate metabolism and plasma HDL2-CHOL levels whereas deep abdominal fat showed significant correlations with HDL2-CHOL levels (P less than 0.05) after correction for indices of carbohydrate metabolism. These results suggest that both disturbances in glucose-insulin homeostasis and abdominal obesity are significantly associated with changes in plasma VLDL-TG and LDL-apo B levels and that these associations are partly independent from each other. These results also indicate that mechanisms other than disturbances in glucose homeostasis and hyperinsulinemia are responsible for the association between the level of deep abdominal fat and plasma HDL2-CHOL levels.     

Giant infectious intracavernous carotid artery aneurysm presenting as intractable epistaxis

Infectious intracavernous carotid artery aneurysms usually present with ophthalmoplegia and/or signs of cavernous sinus thrombosis. We report an unusual case in which a patient with AIDS presented with intractable epistaxis secondary to rupture of a giant infectious intra-cavernous carotid artery aneurysm. Culture of the aneurysm grew mycobacterium avium intracellulare (MAI). The patient was treated successfully by excision of the aneurysm and reconstruction of the internal carotid artery with a saphenous vein interposition graft.     

Methotrexate for the treatment of unruptured tubal pregnancy: a prospective nonrandomized study.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare in a prospective nonrandomized study, the efficacy of 2 methods of administering methotrexate (MTX) in the treatment of ectopic pregnancy (EP): transvaginal injection under sonographic control or intramuscular injection (IM). METHODS: Patients with EP who met specific inclusion criteria for medical treatment were treated with MTX: 63 patients (group 1) were treated by IM and 47 patients (group 2) by transvaginal local injection. In group 1, 50 mg/m2 of MTX was injected intramuscularly; in group 2, transvaginal injection of 1 mg/kg of MTX was injected into the ectopic sac under sonographic control. When an additional dose of MTX was required, it was administrated IM at the dosage of 50 mg/m2 in both groups. RESULTS: The overall success rate, defined by a posttreatment normal hCG level (< 10 mUI/mL) was 71.4% in group 1 versus 91.5% in group 2 (P < 0.01); for patients with hCG levels < 2000 mUI/mL, 83% and 96%, respectively (not significant); for patients with hCG > or = 2000 mUI/mL, 37.5% and 86.4%, respectively (P < 0.01). CONCLUSION: In the medical treatment of EP, the efficacy of MTX is greater when administered by local transvaginal injection than by IM injection. We propose local treatment every time EP can be punctured, especially when hCG levels are > or = 2000 mUI/mL.     

Predictive value of the transtheoretical model to smoking cessation in hospitalized patients with cardiovascular disease.

BACKGROUND: Several authors have questioned the transtheoretical model. Determining the predictive value of each cognitive-behavioural element within this model could explain the multiple successes reported in smoking cessation programmes. The purpose of this study was to predict point-prevalent smoking abstinence at 2 and 6 months, using the constructs of the transtheoretical model, when applied to a pooled sample of individuals who were hospitalized for a cardiovascular event. DESIGN: The study follows a predictive correlation design. METHODS: Recently hospitalized patients (n=168) with cardiovascular disease were pooled from a randomized, controlled trial. Independent variables of the predictive transtheoretical model comprise stages and processes of change, pros and cons to quit smoking (decisional balance), self-efficacy, and social support. These were evaluated at baseline, 2 and 6 months. RESULTS: Compared to smokers, individuals who abstained from smoking at 2 and 6 months were more confident at baseline to remain non-smokers, perceived less pros and cons to continue smoking, utilized less consciousness raising and self-re-evaluation experiential processes of change, and received more positive reinforcement from their social network with regard to their smoke-free behaviour. Self-efficacy and stages of change at baseline were predictive of smoking abstinence after 6 months. Other variables found to be predictive of smoking abstinence at 6 months were an increase in self-efficacy; an increase in positive social support behaviour and a decrease of the pros within the decisional balance. CONCLUSIONS: The results partially support the predictive value of the transtheoretical model constructs in smoking cessation for cardiovascular disease patients.