Molecular characterization of rabies virus isolates from Mexico: implications for transmission dynamics and human risk.

Twenty-eight samples from humans and domestic and wild animals collected in Mexico between 1990 and 1995 were characterized by using anti-nucleoprotein monoclonal antibodies and limited sequence analysis of the nucleoprotein gene. The variants of rabies viruses identified in these samples were compared with other isolates from Mexico and the rest of the Americas to establish epidemiologic links between cases and outbreaks and to increase the understanding of rabies epidemiology in the Western Hemisphere. Antigenic and genetic diversity was found in all samples from dogs and dog-related cases, suggesting a long-term endemic situation with multiple, independent cycles of virus transmission. Two isolates from bobcats were antigenically and genetically homologous to the rabies variant circulating in the Arizona gray fox population, indicating a wider distribution of this variant than previously reported. Rabies isolates from skunks were unrelated to any variant analyzed in this study and represent a previously unrecognized cycle of rabies transmission in skunks in Baja California Sur. Two antigenic and genetic variants co-circulating in southern and eastern Mexico were found in viruses obtained from cases epidemiologically related to vampire bats. These results serve as a baseline for the better understanding of the molecular epidemiology of rabies in Mexico.     

A Randomized Trial of Creatine‐kinase Leak After Rosuvastatin in Elective Percutaneous Coronary Intervention (CLEAR‐PCI)

Objectives

To determine the impact of percutaneous coronary intervention (PCI) performed at the same time of the peak concentration of rosuvastatin to reduce periprocedural myocardial infarction (PMI).

Background

Prior studies suggest that a high dose of statin before PCI reduce periprocedural myocardial infarction. However, there is no information regarding the elective PCI performed at the time of the peak of statin concentration to reduce PMI.

Methods

From 2001 to 2013, at a single center in Brazil we enrolled 544 patients who underwent elective PCI and after exclusions for baseline biases in clinical and angiographic characteristics, yielding 528 patients, we prospectively randomly assigned them to either a high loading dose of Rosuvastatin before PCI (n = 264) or standard treatment (n = 264). After exclusions for biases in procedural characteristics a total of 487 patients underwent to end points analysis. The primary outcome was the incidence of MB fraction of creatine kinase (CK‐MB) greater than three times the upper limit of normal.

Results

The primary end point occurred in 7.6% in the rosuvastatin and 4.8% in the control group (P = 0.200). There was a higher incidence in elevation of CK‐MB than normal baseline in the rosuvastatin (67.1% vs 59.2%, P = 0.701). There was no difference in major adverse event (0% in the rosuvastatin group vs 0.8% in control).

     

A novel germ line mutation in SOX9 causes familial campomelic dysplasia and sex reversal

Mutations in the gene SOX9 result in the syndrome of campomelic dysplasia (CD) which includes sex-reversal in 75% of 46,XY affected individuals. These mutations only affect a single allele of SOX9 suggesting a dominant mode of inheritance for this syndrome. Consequently, CD and autosomal sex reversal may result from haploinsufficiency of SOX9. The SOX9 gene maps to the long arm of human chromosome 17 and translocations in this region also result in CD. We report a family in which there were three affected patients, two of whom showed 46,XY sex-reversal. Interestingly, despite all three patients being heterozygous for a familial mutation in SOX9 (Insertion of a cytosine residue at nucleotide position 1096), their gonadal phenotypes varied widely. The proband was found to have 46,XY true hermaphroditism with ambiguous genitalia. The other two sibs were 46,XY and 46,XX, and both had bilateral ovaries with normal female genitalia. The somatic cells in both parents revealed wild-type SOX9 nucleotide sequences. However, mutational analysis of the SOX9 gene in the father's germ cells revealed they were mosaic for mutant and wild-type sequences. This family is particularly informative as it demonstrates that the same SOX9 mutation can produce very different 46,XY gonadal phenotypes. The range of gonadal morphologies observed may be explained by several possible mechanisms such as variable penetrance of the mutation, increased activity of the non-mutant SOX9 allele or stochastic environmental factors. These results also demonstrate that paternal germ cell mosaicism of a mutant SOX9 sequence can result in a CD phenotype amongst his offspring.      

Renal transplantation across the ABO barrier using A2 kidneys.

BACKGROUND: The waiting list for cadaveric kidney transplantation has continued to grow, and with the relative scarcity of cadaver donors, the median waiting time for patients in the United States increased to 824 days in 1994. The median waiting times for patients with blood groups B or O were 1329 and 1007 days, respectively. Allocation of blood group A2 kidneys (20% of group A) to blood group O and B patients expands their potential donor pool and shortens their waiting time for a kidney transplantation. METHODS: Between May 1991 and June 1998, we transplanted 15 A2 kidneys into 6 blood group O and 9 blood group B patients. Anti-A isoagglutinins were measured before transplantation, and patients with anti-A1 titers > or = 1:8 underwent plasmapheresis (PP). RESULTS: One patient with high titer anti-A antibodies, who did not receive PP, lost her allograft because of hyperacute rejection. Allograft function was excellent in the remaining 14 patients, with a mean serum creatinine level of 1.7 (+/-0.89) mg/dl at 1 month and 1.3 (+/-0.34) mg/dl at 1 year. The actuarial 1-year graft survival rate was 93.3+/-6.4% and the patient survival rate was 100%. CONCLUSION: We conclude that the allocation of blood group A2 kidneys for blood group O and B recipients is a practical way to expand the donor pool for these transplant candidates. PP may be important for reducing the levels of anti-A1 and anti-A2 antibodies and for reducing the risk of hyperacute rejection. Splenectomy seems to be unnecessary.     

Safety of dobutamine-atropine stress echocardiography: A prospective experience of 4,033 consecutive studies.

Dobutamine-atropine stress echocardiography (DASE) is an established method and has been shown to be accurate for the detection of coronary artery disease. Still, there are few large clinical studies that analyze the safety of DASE in general or the safety of performing it on an ambulatory basis. Most studies use a target heart rate as the primary end point regardless of whether asymptomatic ischemia occurs. Such studies have shown a serious cardiac event rate of approximately 0.3%. We prospectively studied 4,033 consecutive patients on an ambulatory basis and in the hospital with the use of DASE from July 1991 to December 1998. All tests were performed by an experienced physician, and all clinical and DASE data were stored in a large database organized at the beginning of the study. Dobutamine was infused in scalar doses of 5, 10, 20, 30, and 40 microg/kg per minute in 3-minute stages. Development of a new wall motion abnormality, achievement of 85% of target heart, and end of the DASE infusion protocol were used as an end point. If 85% of the target heart rate was not achieved, atropine was infused up to 1 mg in the absence of myocardial ischemia, which was used in 1,280 studies. There were 3,645 diagnostic tests, and 388 (10%) were found to be nondiagnostic. This result was due to poor image quality in 115 (3%), end of protocol in negative-submaximal examinations in 124 (3%), and limiting side effects in 149 (4%). Thirty-seven percent of the tests showed positive results for myocardial ischemia. Major test-related cardiac complications occurred in 10 (0.25%) patients and included 1 ventricular fibrillation, 1 case of myocardial infarction, and 8 cases of sustained ventricular tachycardia. Atropine poisoning was observed in 5 (0.12%) patients. No deaths occurred as a direct or indirect consequence of DASE. We conclude that dobutamine-atropine stress echocardiography is a reasonably safe method for detection of coronary artery disease in the hospital or in an ambulatory basis. The use of new wall motion abnormality as 1 of the end points may prevent further ischemia-related complications.     

Correction to: Genetic Analysis of Hereditary Ataxias in Peru Identifies SCA10 Families with Incomplete Penetrance

The Cerebellum - The original version of this article unfortunately contained some mistakes in Table 2. The additional row (just above SCA2) with the following information “SCA1, 1(1), 1, 50,...     

Is duplex follow-up cost-effective in the first year after carotid endarterectomy?

Recent reports have suggested that duplex scanning is an ideal method to noninvasively assess the incidence of recurrent carotid stenosis. However, the timing and frequency of the follow-up studies are controversial. In the present study, 150 patients underwent 173 carotid endarterectomy procedures over a 2 year period. In the postoperative period, a total of 210 duplex studies were carried out on 117 carotid arteries. 21.4 percent of the 117 arteries studied had recurrent stenosis of 16 percent or greater at a mean postoperative follow-up of 15.2 +/- 3 months. Recurrent stenoses were detected early after operation; 96 percent were detected at or before 15 months postoperatively. Patients with recurrent stenoses remained stable and had infrequent symptoms. Several risk factors placed the patient at increased risk for recurrent carotid stenosis: presence of contralateral disease (defined as stenosis of 50 percent or greater), use of tacking sutures, and continued smoking in the postoperative period. Although it remains important for researchers to thoroughly investigate the natural history of atherosclerosis of the extracranial carotid artery, including those changes that occur after carotid endarterectomy, our results indicate that frequent duplex scanning in the first postoperative year is unnecessary and is not cost-effective. Duplex follow-up studies 1 and 12 months after carotid endarterectomy are sufficient for assessing the problem of recurrent stenosis in the first postoperative year.     

IgA肾病的治疗进展

IgA 肾病是最常见的原发性肾小球疾病,由于其发病机制尚未明确,目前仍无特异性治疗药物.临床上的治疗目标是有效降低蛋白尿,控制血压和(或) 高尿酸并减少肾组织进一步损伤,维持肾功能稳定.对反复发作的镜下血尿患者,扁桃体切除术作为治疗的一种手段;对单纯性血尿和病理改变较轻者,主要加强随访观察;对于有尿蛋白和(或)高血压的缓慢进展的IgA肾病,血管紧张素转化酶抑制剂和血管紧张素受体拮抗剂可用于大部分病例,必要时可使用糖皮质激素,也可应用细胞毒性药物或吗替麦考酚酯等免疫抑制剂进行治疗;病情进展较快的高危患者,可用糖皮质激素冲击治疗,或使用细胞毒药物或免疫抑制剂等强化治疗.     

P2Y12 inhibitors for the neurointerventionalist

The use of antiplatelets is widespread in clinical practice. However, for neurointerventional procedures, protocols for antiplatelet use are scarce and practice varies between individuals and institutions. This is further complicated by the quantity of antiplatelet agents which differ in route of administration, dosage, onset of action, efficacy and ischemic and hemorrhagic complications. Clarifying the individual characteristics for each antiplatelet agent, and their associated risks, will increasingly become relevant as the practice of mechanical thrombectomy, stenting, coiling and flow diversion procedures grows. The aim of this review is to summarize the existing literature for the use of P2Y12 inhibitors in neurointerventional procedures, examine the quality of the evidence, and highlight areas in need of further research.