Very high coronary artery calcium score with normal myocardial perfusion SPECT imaging is associated with a moderate incidence of severe coronary artery disease.

PURPOSE: Myocardial perfusion imaging (MPI) has limitations in the presence of balanced multivessel disease (MVD) and left main (LM) coronary artery disease, occasionally resulting in false-normal results despite the high cardiovascular risk associated with this condition. The purpose of this study was to assess the incidence of severe coronary artery disease (CAD) in the presence of a very high Agatston coronary artery calcium (CAC) score (>1,000) in stable symptomatic patients without known CAD but with normal MPI results. METHODS: A total of 2,659 prospectively acquired consecutive patients were referred for MPI and evaluation of CAC score by CT. Of this patient population, 8 % (222/2,659) had ischemia without myocardial infarction (MI) on MPIand 11 % (298/2,659) had abnormal MPI (MI and/or ischemia). On presentation 1 % of the patients (26/2,659) were symptomatic, had a CAC score >1,000 and normal MPI results. The definition of normal MPI was strict and included a normal hemodynamic response without ischemic ECG changes and normal imaging, particularly absence of transient ischemic dilation. All of these 26 patients with a CAC score >1,000 and normal MPI findings underwent cardiac catheterization. RESULTS: Of these 26 patients, 58 % (15/26) had severe disease (≥70 % stenosis) leading to revascularization. Of this group, 47 % (7/15) underwent percutaneous intervention, and 53 % (8/15) underwent coronary artery bypass grafting. All of these 15 patients had either MVD (14/15) or LM coronary artery disease (1/15), and represented 0.6 % (15/2,659) of all referred patients (95 % CI 0.3 - 0.9 %). The majority, 90 % (8/9), had severe CAD with typical chest pain. CONCLUSION: A very high CAC score (>1,000) with normal MPI in a small subset of symptomatically stable patients was associated with a moderate incidence of severe CAD (95 % CI 37 - 77 %). Larger studies and/or a meta-analysis of small studies are needed to more precisely estimate the incidence of CAD in this population. This study also supports the concept that a normal MPI result in patients with severe CAD may be due to balanced MVD.

In vivo experimental evidence that the major metabolites accumulating in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency induce oxidative stress in striatum of developing rats: a potential pathophysiological mechanism of striatal damage in this disorder.

3-Hydroxy-3-methylglutaryl-CoA lyase (HL) deficiency is a genetic disorder biochemically characterized by predominant accumulation of 3-hydroxy-3-methylglutaric (HMG) and 3-methylglutaric (MGA) acids in tissues and biological fluids of affected individuals. Clinically, the patients present neurological symptoms and basal ganglia injury, whose pathomechanisms are partially understood. In the present study, we investigated the ex vivo effects of intrastriatal administration of HMG and MGA on important parameters of oxidative stress in striatum of developing rats. Our results demonstrate that HMG and MGA induce lipid and protein oxidative damage. HMG and MGA also increased 2',7'-dichlorofluorescein oxidation, whereas only HMG elicited nitric oxide production, indicating a role for reactive oxygen (HMG and MGA) and nitrogen (HMG) species in these effects. Regarding the enzymatic antioxidant defenses, both organic acids decreased reduced glutathione concentrations and the activities of superoxide dismutase and glutathione reductase and increased glutathione peroxidase activity. HMG also provoked an increase of catalase activity and a diminution of glucose-6-phosphate dehydrogenase activity. We finally observed that antioxidants fully prevented or attenuated HMG-induced alterations of the oxidative stress parameters, further indicating the participation of reactive species in these effects. We also observed that MK-801, a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, prevented some of these effects, indicating the involvement of the NMDA receptor in HMG effects. The present data provide solid evidence that oxidative stress is induced in vivo by HMG and MGA in rat striatum and it is presumed that this pathomechanism may explain, at least in part, the cerebral alterations observed in HL deficiency.

Periovulatory Hormonal Profiles after Estrus Induction and Conception Rate by Fixed-Time AI in Payoya Goats during the Anestrous Season.

Sexual activity in domestic goats is positively influenced by reducing the photoperiod. Various protocols have therefore been developed in goats for the induction and synchronization of estrus during those months in which their sexual activity is reduced. The present observational study evaluates the periovulatory hormonal profile in Payoya goats (n = 24), during a non-favorable photoperiod (i.e., spring), being treated for estrus induction. The treatment comprised the vaginal insertion of sponges impregnated with progestogen (fluorogestone acetate, FGA), together with cloprostenol and equine chorionic gonadotrophin (eCG), 48 h before the end of the treatment. When the treatment ended, the plasma concentrations of the LH, FSH, progesterone and estradiol were determined. The goats were inseminated 46 h after the sponge withdrawal, and a pregnancy diagnosis was carried out 40-45 days after the insemination. Various parameters were monitored, such as the peaks of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol, and their respective intervals, in reference to the time of the sponge withdrawal. The conception rate was 62.5%, and the kidding rate was 50%. The results record the hormonal release pattern after the estrus synchronization treatment based on the FGA, and the differences between the pregnant and non-pregnant goats. The findings suggest that the LH peak produced after the estrus synchronization treatment, both in terms of the amplitude and the time of increment, is involved in the reproductive failure detected.

Colpocleisis in vesico-vaginal radiation fistula.

OBJECTIVE: To assess Latzko's colpocleisis with bilateral Martius flap as a solution for vesico vaginal fistula secondary to radiotherapy. METHOD: 65 year old woman with past medical history of cervix adenocarcinoma treated with hysterectomy, pelvic radiotherapy and brachytherapy. She also had terminal colostomy for recto-vaginal fistula. She complained of a 2-year history of continuous urinary escape through vagina. On cistoscopy, the ureteral orifices were close to the loss of substance. Colpocleisis following Latzko's technique was performed. RESULTS: Complete resection of the fistulous tract and tension free closure is a surgical challenge not always achieved, and with a high recurrence rate. Latzko's colpocleisis is a simple and safe option in patients that have previously undergone a hysterectomy. Bilateral Martius flap increases vascular support of the affected tissues, which is of pivotal importance in patients subjected to radiotherapy. CONCLUSION: Latzko's colpocleisis is a valid therapeutic option in those histerectomised patients with vesico vaginal fistulas due to radiotherapy who are not eligible for fistulorraphy.

Disturbance of the glutamatergic system by glutaric acid in striatum and cerebral cortex of glutaryl-CoA dehydrogenase-deficient knockout mice: possible implications for the neuropathology of glutaric acidemia type I.

The role of excitotoxicity on the neuropathology of glutaric acidemia type I (GA I) is still under debate. Therefore, in the present work, we evaluated glutamate uptake by brain slices and glutamate binding to synaptic membranes, as well as glutamine synthetase activity in cerebral cortex and striatum from glutaryl-CoA dehydrogenase deficient (Gcdh(-/-)) mice along development (7, 15, 30 and 60 days of life) in the hopes of clarifying this matter. We also tested the influence of glutaric acid (GA) added exogenously on these parameters. [(3)H]Glutamate uptake was not significantly altered in cerebral cortex and striatum from Gcdh(-/-) mice, as compared to WT mice. However, GA provoked a significant decrease of [(3)H]glutamate uptake in striatum from both WT and Gcdh(-/-) mice older than 7 days. This inhibitory effect was more pronounced in Gcdh(-/-), as compared to WT mice. The use of a competitive inhibitor of glutamate astrocytic transporters indicated that the decrease of [(3)H]glutamate uptake caused by GA was due to the competition between this organic acid and glutamate for the same astrocytic transporter site. We also found that Na(+)-dependent [(3)H]glutamate binding (binding to transporters) was increased in the striatum from Gcdh(-/-) mice and that GA significantly diminished this binding both in striatum and cerebral cortex from Gcdh(-/-), but not from WT mice. Finally, we observed that glutamine synthetase activity was not changed in brain cortex and striatum from Gcdh(-/-) and WT mice and that GA was not able to alter this activity. It is therefore presumed that a disturbance of the glutamatergic neurotransmission system caused by GA may potentially be involved in the neuropathology of GA I, particularly in the striatum.