Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil): possible role in hypersensitivity reactions.

BACKGROUND: Pegylated liposomal doxorubicin (Doxil) has been reported to cause immediate hypersensitivity reactions (HSRs) that cannot be explained as IgE-mediated (type I) allergy. Previous in vitro and animal studies indicated that activation of the complement (C) system might play a causal role in the process, a proposal that has not been tested in humans to date. PATIENTS AND METHODS: Patients with solid tumors (n = 29) treated for the first time with Doxil were evaluated for HSRs and concurrent C activation. HSRs were classified from mild to severe, while C activation was estimated by serial measurement of plasma C terminal complex (SC5b-9) levels. Increases in SC5b-9 were compared in patients with or without reactions, and were correlated with Doxil dose rate. RESULTS: Moderate to severe HSRs occurred in 45% of patients. Plasma SC5b-9 at 10 min after infusion was significantly elevated in 92% of reactor patients versus 56% in the non-reactor group, and the rise was greater in reactors than in non-reactors. We found significant association between C activation and HSRs, both showing direct correlation with the initial Doxil dose rate. CONCLUSIONS: C activation may play a key role in HSRs to Doxil. However, low-level C activation does not necessarily entail clinical symptoms, highlighting the probable involvement of further, as yet unidentified, amplification factors.     

Genotypic distribution of human papillomavirus and phylogenetic analysis of E6 and E7 gene of HR-HPV variants isolated from Pakistani population

High-risk-human papillomavirus (HR-HPV)-induced cervical cancer is the second most common cause of death among females worldwide. HPV16 is the most prevalent HR-HPV infection worldwide. This study found the genotypic distribution of HR-HPV in the local population and investigated the sequence variations among the E6 and E7 oncogenes of the local HPV16 genotype to the E6 and E7 oncogenes of the foreign HPV16 genotypes and constructed a phylogenetic relationship based on nucleotide sequence comparison among the variants identified in our study along with previously reported isolates that were obtained from different regions of the world. The samples were collected from patients with cervical cancer. Genomic DNA was extracted, and HR-HPV genotypes were determined using real-time PCR. The HPV16 E6 and E7 genes were amplified and sequenced. A HPV16 phylogenetic tree was constructed using the maximum likelihood method with MEGA 7. HPV16 was the most prevalent human papillomavirus (HPV) type identified in the present study. HPV16 isolates belonged to the A1 sublineage of the European branch. Twenty-one nucleotide sequences were included in this analysis. The first, second, and third codon positions are also included. The final dataset included 776 positions.     

The cellulose synthase BcsA plays a role in interactions of Salmonella typhimurium with Acanthamoeba castellanii genotype T4

Parasitology Research - Pathogenic bacteria share their natural habitat with many other organisms such as animals, plants, insects, parasites and amoeba. Interactions between these organisms...     

Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab

Pharmacological inhibition of VEGF-A has proven to be effective in inhibiting angiogenesis and vascular leak associated with cancers and various eye diseases. However, little information is currently available on the binding kinetics and relative biological activity of various VEGF inhibitors. Therefore, we have evaluated the binding kinetics of two anti-VEGF antibodies, ranibizumab and bevacizumab, and VEGF Trap (also known as aflibercept), a novel type of soluble decoy receptor, with substantially higher affinity than conventional soluble VEGF receptors. VEGF Trap bound to all isoforms of human VEGF-A tested with subpicomolar affinity. Ranibizumab and bevacizumab also bound human VEGF-A, but with markedly lower affinity. The association rate for VEGF Trap binding to VEGF-A was orders of magnitude faster than that measured for bevacizumab and ranibizumab. Similarly, in cell-based bioassays, VEGF Trap inhibited the activation of VEGFR1 and VEGFR2, as well as VEGF-A induced calcium mobilization and migration in human endothelial cells more potently than ranibizumab or bevacizumab. Only VEGF Trap bound human PlGF and VEGF-B, and inhibited VEGFR1 activation and HUVEC migration induced by PlGF. These data differentiate VEGF Trap from ranibizumab and bevacizumab in terms of its markedly higher affinity for VEGF-A, as well as its ability to bind VEGF-B and PlGF.     

Anesthesia for children with mitochondrial disorders: a national survey and review

Purpose

Mitochondrial diseases are a heterogeneous group of disorders. Patients with such diseases often need general anesthesia for diagnostic procedures and surgery; guidelines are lacking for the anesthetic care of these patients.

Methods

We conducted a survey to investigate the current practices of pediatric anesthesiologists in the US in order to determine and document current practice. The survey consisted of twenty questions, including two demographic questions. A link to the survey was sent via email to members of the Society for Pediatric Anesthesia (2440), and was available online for 14 weeks.

Results

Only 503 completed the survey: a response rate of 20.61 %. Among the responders, 93.2 % had children with mitochondrial disorders among their patients, but only 11 % had institutional guidelines for such cases in place. Among the responders, 80.3 % used the standard nil per os (NPO) status guidelines, while the rest give intravenous dextrose solution once NPO was in effect. Only 18.3 % took precautions for malignant hyperthermia during treatment. The majority of the practitioners chose sevoflurane as the safest inhaled agent for induction and maintenance (89.7 and 78.5 %, respectively). Regional anesthesia was deemed safe by 97.3 % of the responders. Lactated Ringer’s solution was considered safe for these children by 49 %; only 47.8 % used dextrose-containing fluids for fluid replacement. The blood glucose was monitored by 72.7 %, and the majority (85 %) of this monitoring was done in a postanesthesia care unit.

Conclusion

Although the response rate was low, the majority of the responders provide care to these children routinely, so it can be inferred that the results of this survey are the closest published results to the true trend.