Low Incidence of Pseudoprogression by Imaging in Newly Diagnosed Glioblastoma Patients Treated With Cediranib in Combination With Chemoradiation

Background.

Chemoradiation (CRT) can significantly modify the radiographic appearance of malignant gliomas, especially within the immediate post-CRT period. Pseudoprogression (PsP) is an increasingly recognized phenomenon in this setting, and is thought to be secondary to increased permeability as a byproduct of the complex process of radiation-induced tissue injury, possibly enhanced by temozolomide. We sought to determine whether the addition of a vascular endothelial growth factor (VEGF) signaling inhibitor (cediranib) to conventional CRT had an impact on the frequency of PsP, by comparing two groups of patients with newly diagnosed glioblastoma before, during, and after CRT.

Methods.

All patients underwent serial magnetic resonance imaging as part of institutional review board-approved clinical studies. Eleven patients in the control group received only chemoradiation, whereas 29 patients in the study group received chemoradiation and cediranib until disease progression or toxicity. Response assessment was defined according to Response Assessment in Neuro-Oncology criteria, and patients with enlarging lesions were classified into true tumor progressions (TTP) or PsP, based on serial radiographic follow-up.

Results.

Two patients in the study group (7%) showed signs of apparent early tumor progression, and both were subsequently classified as TTP. Six patients in the control group (54%) showed signs of apparent early tumor progression, and three were subsequently classified as TTP and three as PsP. The frequency of PsP was significantly higher in the control group.

Conclusion.

Administration of a VEGF inhibitor during and after CRT modifies the expression of PsP by imaging.     

A comparison of U.S. and Canadian cardiac catheterization practices in detecting severe coronary artery disease after myocardial infarction: efficiency, yield and long-term implications.

OBJECTIVES: We sought to compare U.S. and Canada's post-myocardial infarction (MI) cardiac catheterization practices in the detection of severe coronary artery disease (CAD). BACKGROUND: Little is known about the efficiency with which the aggressive post-MI catheterization strategy observed in the U.S. detects severe CAD compared with the more conservative strategy observed in Canada. METHODS: From the U.S. and Canadian patients who had participated in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries trial (n = 22,280, 11.5% Canadian), we examined the frequency of in-hospital cardiac catheterization, the prevalence of severe CAD observed at catheterization (diagnostic efficiency) and the total number of MI patients with severe CAD identified (diagnostic yield). RESULTS: The rate of catheterization in the U.S. was more than 2.5 times that in Canada (71% vs. 27%, respectively, p < 0.001). With identical prevalences of severe CAD at catheterization (17%) in the two countries, the higher frequency of catheterization in the U.S. resulted in the identification of more than two and a half times as many cases of severe CAD compared with Canada (12 severe CAD cases identified per 100 post-MI patients in the U.S., vs. 4.6 per 100 in Canada). If considered in isolation, we estimated that these differences in severe disease detection might effect a small long-term survival advantage in favor of the U.S. strategy (estimated 5.0 lives saved per 1,000 MI patients). CONCLUSIONS: Canada's more restrictive post-MI cardiac catheterization strategy is no more efficient in identifying severe CAD than the aggressive U.S. strategy, and may fail to identify a substantial number of post-MI patients with high risk coronary anatomy. The long-term impact of these differences in practice patterns requires further evaluation.     

Number and timing of antenatal HIV testing: Evidence from a community-based study in Northern Vietnam

Background  

HIV testing for pregnant women is an important component for the success of prevention of mother-to-child transmission of HIV (PMTCT). A lack of antenatal HIV testing results in loss of benefits for HIV-infected mothers and their children. However, the provision of unnecessary repeat tests at a very late stage of pregnancy will reduce the beneficial effects of PMTCT and impose unnecessary costs for the individual woman as well as the health system. This study aims to assess the number and timing of antenatal HIV testing in a low-income setting where PMTCT programmes have been scaled up to reach first level health facilities.     

Nurse practitioners in primary care iv. Impact of an interdisciplinary team on attitudes of a rural population.

Attitudes toward the expanded role of nurse practitioners in primary care (family practice nurses) have been determined for persons from a semirural area who chose as their principal souce of care an interdisciplinary family medical centre (FMC) incorporating two nurse practitioners, and those for whom the FMC was not the usual source of care. Data were obtaine using"before-and-after" structured interviews of a random sample of persons living in a southern Ontario township. Slowly evolving, nonsignificant trends of greater acceptance were observed among patiens who had dealth with family practice nurses. The greatest change observed was an increased acceptance of the nnurse by FMC users as the person who would be contacted as a second choice if theirfirst choice, usually a physician, could not be reached in specific worrry-inducing situations. FMC users depended more on nurses to provide information. A conclusion of increased general acceptance of the family practive nurse by FMC users is supported by a 34 per cent higher use of nurses by FMC patients compared to other persons of comparable characteristics living in the same community.     

Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States.

Tuberous sclerosis complex is an autosomal dominant neurocutaneous disorder marked by hamartoma growth in multiple organ systems. We performed mutational analyses on 325 individuals with definite tuberous sclerosis complex diagnostic status. We identified mutations in 72% (199/257) of de novo and 77% (53/68) of familial cases, with 17% of mutations in the TSC1 gene and 50% in the TSC2 gene. There were 4% unclassified variants and 29% with no mutation identified. Genotype/phenotype analyses of all observed tuberous sclerosis complex findings in probands were performed, including several clinical features not analyzed in two previous large studies. We showed that patients with TSC2 mutations have significantly more hypomelanotic macules and learning disability in contrast to those with TSC1 mutations, findings not noted in previous studies. We also observed results consistent with two similar studies suggesting that individuals with mutations in TSC2 have more severe symptoms. On performing meta-analyses of our data and the other two largest studies in the literature, we found significant correlations for several features that individual studies did not have sufficient power to conclude. Male patients showed more frequent neurologic and eye symptoms, renal cysts, and ungual fibromas. Correlating genotypes with phenotypes should facilitate the disease management of tuberous sclerosis complex.     

Multiple sclerosis and HLA: is the susceptibility gene really HLA-DR or -DQ?

Seventy-one patients with multiple sclerosis (MS) were classified into four subgroups according to the clinical pattern of their disease; their HLA-DR and DQ polymorphisms were defined by serological methods and analysis of Taq1 digestion fragments hybridizing with DRB, DQA, and DQB cDNA probes. The frequencies of the polymorphisms in the patients were compared with those of 100 control subjects. The frequencies of a 3.25-kb fragment from Mspl digests of genomic DNA which hybridized to DQA were also defined in the same groups of patients and control subjects. HLA-DR2 (DRw 15 subtype) and the associated HLA-DQw6 were observed in significant excess in the patients compared with the normal subjects (63% vs. 32% for DRw15; 65% vs. 42% for DQw6). There were no significant differences in the distribution of the DR or DQ alleles between the groups of patients showing different clinical patterns of disease, nor was there an excess in the patients of DQw8 and DQw9 which share hypervariable region sequences of the DQB chain in common with DQw6. The results argue against two recently proposed hypotheses of MS. First, they are not consistent with the proposal that susceptibility to MS is associated with expression of a hypervariable region of DQB shared by DQw6, 8, and 9. Second, they do not support the concept that primarily chronic progressive and relapsing/remitting MS are two immunogenetically distinct disease entities. Our evidence is consistent with the hypothesis that one of the true disease susceptibility genes for MS lies elsewhere within the HLA region and in Northern European populations is found in significant association with DRw15 and DQw6.     

C4 and HLA haplotypes associated with partial inhibition of anti-Rg and anti-Ch

Rg and Ch typing was performed, by serum inhibition, on 145 families that had been typed for HLA/C4/BF/C2 with a view to assessing partial inhibition (p.i.) of anti-Rg/Ch and its haplotype associations. Rg p.i. was found predominantly with the C4A*3A*2,B*QO homoduplicated C4 haplotype and BFF. The original type of Ch p.i. (Nordhagen et al., 1980) was closely associated with the allotype C4B 2, which also occasionally exhibited complete inhibition (c.i.), but this Ch p.i. was also found with the C4A*1,B*QO haplotype (Rittner et al., 1984a). The second type of Ch p.i. (Giles, 1984) was closely associated with the C4B 1 allotype most frequently in the haplotype C4A*6,B*1 but also with C4A*3,B*1. Both types of Ch p.i. are usually found with BF S. The present data indicate that the determinants of Rg and Ch are not directly related to any particular C4 allotype or extended haplotype. Further examples of C4A 1 with Ch and C4B 5 without Ch determinants have been detected and theoretical considerations are discussed as to how they might have arisen from unequal crossovers in homologous regions that result in hybrid protein molecules.