Efficacy of Change to New P2Y12 Receptor Antagonists in Patients High on Treatment Platelet Reactivity Undergoing Percutaneous Coronary Intervention.

Selective intensification of platelet inhibition may improve high on treatment platelet reactivity (HPR). We evaluated the efficacy of dual-antiplatelet therapy, including clopidogrel (CPG), compared to new P2Y12-receptor antagonists in patients with HPR undergoing percutaneous coronary intervention, regarding the outcome of composite major adverse cardiac events (MACEs, including death, acute coronary syndrome [ACS], and stent restenosis). The presence of HPR (71 of 181 patients) almost doubled the risk of MACEs. The new antiplatelet agent reduced MACEs (45.8%, 26%, and 16.7% for CPG, prasugrel, and ticagrelor [TGL]; RR 0.36; 0.13-0.98, P = .03, TGL), specifically in patients with ACS. Failure to reduce HPR after the antiplatelet change and diabetes were independent predictors for MACEs. The HPR was early and effectively reduced after changing the antiplatelet therapy, but the intensity of this reduction did not significantly decrease the risk of MACEs. These findings support the benefit of HPR-guided intensification of platelet inhibition. Whether the intensity of this reduction improves the patient's clinical outcomes deserves further investigation.

Trisomy of the short arm of chromosome 5 due to a de novo inversion and duplication (5)(p15.3 p13.3).

Partial trisomies of the short arm of chromosome 5 are uncommon. The first description was made by Lejeune et al., in 1964. It has been suggested that the critical region for 5p trisomy syndrome lies between 5p10 and 5p13. We report on a Mexican girl who developed severe mental retardation and generalized tonic clonic seizures at age 1 year. On physical examination at age 5 years, she had macrodolichocephaly, upslanted palpebral fissures, bilateral inner epicanthic folds, low nasal root, and malformed ears with posterior rotation which are clinical characteristics of 5p trisomy syndrome. The cytogenetic study with G bands and FISH with painting for chromosome 5 and with the cri-du-chat 5p15 unique sequence probe showed a duplication and inversion of 5p [46,XX, dup(5)(p15.3 p13.3)] which overlaps with the critical region for 5p trisomy syndrome. Our patient shares clinical characteristics with the patients described in the literature with involvement of this critical region. Both parents have normal karyotypes indicating the rearrangement is de novo. Only one patient has been reported in the literature with the same cytogenetic rearrangement as our patient, but this patient had a different phenotype. Since they only performed conventional cytogenetics and we performed FISH to confirm the diagnosis, the differences in the phenotypes could be explained by the presence of other genes involved in the rearrangement. The combined use of conventional and molecular cytogenetics in this case allows a more precise diagnosis and furthers knowledge in phenotype/genotype correlation.

Carrier detection and prenatal molecular diagnosis in a Duchenne muscular dystrophy family without any affected relative available.

In this paper we report a family where the affected DMD patients were not available for study and a molecular strategy was used for female carriers detection and for prenatal diagnosis. Linkage analysis was performed with two markers within the DMD gene, in all family members screened. DMD markers used (pERT87.8/Taq1 and pERT87.15/Xmn1) seemed not to be informative because the propositas mother (II-2) was homozygous for the minor allele at each marker (T2 and X2), however, the proposita and one sister carried only the major allele, which was inherited from the father. These results suggested that a deletion involving both markers could be present, and was inherited from the mother to both daughters. Quantitative multiplex PCR confirmed the deletion in female carriers, involving at least exons 12 to 17. DNA studies of cultured amniotic fluid cells at 14 weeks gestation, by amplification of specific Y-chromosome sequences, followed by multiplex PCR, lead to the diagnosis of a male fetus affected by DMD.

High frequency of de novo deletions in Mexican Duchenne and Becker muscular dystrophy patients. Implications for genetic counseling.

Duchenne muscular dystrophy (DMD) is the most common lethal hereditary neuromuscular disease. As there is no effective treatment, accurate carrier detection is essential for genetic counseling and prevention. Although linkage analysis has been widely used for this purpose, being an indirect analysis it has several limitations. Using linkage analysis for carrier detection, we found serious limitations, mainly because 82.9% of all proposita were isolated cases. We used quantitative polymerase chain reaction for direct carrier detection in families with exon deletions and found a higher than expected frequency of de novo deletions (62.2%). Furthermore, only 20.7% of the mothers of isolated deletion DMD/Becker muscular dystrophy (BMD) patients were found to be carriers. This result suggests that the Mexican population has a high frequency of de novo DMD mutations.

Artérias da base do encéfalo de cäes (Canis familiaris, Linnaeus, 1758). I. Estudo anatômico de suas origens e comportamento / Arteries of the basis of the encephalon in dogs (Canis familiaris, Linnaeus, 1758). I. Anatomical study of sources and behaviour

Foram utilizadas 43 peças de cäes sem raça definida, sendo 30 delas dissecadas e as 13 restantes submetidas a processo de corrosäo. As artérias da base do encéfalo estudadas estäo na dependência de duas grandes fontes principais representadas, uma delas pela artéria basilar (sistema vértebro-basilar) e, a outra, pelas artérias carótidas internas esquerda e direita (sistema carótico); considerou-se, ainda, a possibilidade de ocorrência de fonte auxiliar, representada pelas anastomoses existentes entre a artéria maxilar e a artéria carótida interna. A particular disposiçäo dos ramos das artérias carótidas internas e dos ramos terminais da artéria basilar determina formaçäo de um circuito arterial do encéfalo que, a partir da divisäo da artéria carótida interna, de ambos os lados, em seus ramos terminais, rostral e caudal, apresenta-se rostralmente de modo invariável, em pequeno arco ou ferradura de concavidade caudal; caudalmente de forma variada, constitui figura piriforme (56,6 por cento) ou poligonal (43,4 por cento) constituída, rostralmente, pelas artérias cerebrais rostrais esquerda e direita, lateralmente, pelos ramos rostral e caudal das artérias carótidas internas esquerda e direita e, caudolateralmente, pelos ramos terminais (à esquerda e à direita) da artéria basilar. O padräo vascular da artérias da base do encéfalo dos cäes estudados situa-se entre os tipos 2alfa e 2beta, referidos por De Vriese3 (1905) e entre os estágios médio e final de seu desenvolvimento filogenético, considerado por Testut13 (1911)

Artérias da base do encéfalo de cäes (Canis familiaris, Linnaeus, 1758). II. Formaçäo e comportamento do circuito arterial do encéfalo / Arteries of the basis of the encephalon in dogs (Canis familiaris, Linnaeus, 1758). II. Formation and behaviour of the encephalon arterial circuit

Foram estudadas, mediante dissecaçäo, 30 peças de cäes SRD (sem raça definida), com o objetivo de melhor conhecer particularidades do comportamento das artérias da base do encéfalo. Nestas preparaçöes observou-se que a particular disposiçäo dos ramos terminais das artérias carótidas internas e basilar determina a formaçäo de um CIRCUITO ARTERIAL, que contorna a hipófise e o quiasma óptico. Esta formaçäo, a partir da divisäo da artéria carótida interna, de ambos os lados, em seus ramos terminais rostral e caudal, apresenta-se, de modo invariável, em pequeno arco ou ferradura de concavidade caudal; caudalmente, de forma variada, constitui figura piriforme (56,6 por cento) ou poligonal (43,3 por cento) representada rostralmente, pelas artérias cerebrais rostrais esquerda e direita; lateralmente, pelos ramos terminais rostral e caudal das artérias carótidas internas esquerda e direita; e caudolateralmente, pelos ramos terminais (à esquerda e à direita) da artéria basilar

Long-acting estrogenic responses of estradiol fatty acid esters.

Estradiol esters at C-17 and C-3 with palmitic, stearic and oleic acids were chemically synthesized and then evaluated for their long-acting estrogenic responses in ovariectomized rats. The duration of the biological effects was measured after a single subcutaneous dose of 0.1 mumol of each ester and compared with those observed with 17 beta-estradiol, estradiol 3-benzoate and estradiol 17-enanthate. Vaginal citology, uterophyc action, serum gonadotropins inhibition and 17 beta-estradiol levels were measured 0, 5, 10, 20, 30 and 60 days after injection. The results disclosed that most of the estradiol derivatives evaluated exhibited a long-acting estrogenic action. However, the monoesters at C-17 showed longer effects that monoesters at C-3, while the estradiol diesters exhibited the shortest effects. In addition as shown by its low serum levels, all estradiol esters with unsaturated fatty acids show a decreased E2 absorption. The overall results indicated that esterification of E2 with long chain fatty acids provided long-acting properties to it, being higher with C-17 esters. Whether some of these compounds could be employed in substitutive endocrine therapy remains to be established.

Synthesis and biological assessment of long-acting estradiol fatty acid esters in ovariectomized rats.

Diesters of 17 beta-estradiol using palmitic acid (16:0) and oleic acid (18:1, cis-9-Octadecenoic acid) have been synthesized for potential evaluation as long-acting compounds. Female castrated rats were injected 1 mumol of estradiol dipalmitate and estradiol dioleate, using estradiol benzoate and estradiol enanthate as controls. Biological activity was determined by uterine wet weight and uterine diameter as well as on the suppression of serum anterior pituitary gonadotropins. A delayed absorption of estradiol was observed after administration of both diesters which was well correlated with the duration of biological effects. The data demonstrate that esterification with palmitic or oleic acids at 3 and 17 positions provides long-acting properties to 17 beta-estradiol, which could be applied in substitutive therapy and or in hormonal contraception.