Interventional Anesthetic Methods for Pain in Hematology/Oncology Patients.

This article reviews anesthetic interventional approaches to the management of pain in hematology and oncology patients. It includes a discussion of single interventions including peripheral nerve blocks, plexus injections, and sympathetic nerve neurolysis, and continuous infusion therapy through implantable devices, such as intrathecal pumps, epidural port-a-caths, and tunneled catheters. The primary objective is to inform members of hematology and oncology care teams regarding the variety of interventional options for patients with cancer-related pain for whom medical pain management methods have not been effective.

Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has gained attention as a key regulator of serum low density lipoprotein cholesterol (LDL-C) levels. This novel protease causes the degradation of hepatic low density lipoprotein receptors. In humans, gain-of-function mutations in PCSK9 cause a form of familial hypercholesterolemia, whereas loss-of-function mutations result in significantly decreased LDL-C levels and cardiovascular risk. Previous studies have demonstrated that statins upregulate PCSK9 mRNA expression in cultured cells and animal models. In light of these observations, we studied the effect of atorvastatin on circulating PCSK9 protein levels in humans using a sandwich ELISA to quantitate serum PCSK9 levels in patients treated with atorvastatin or placebo for 16 weeks. We observed that atorvastatin (40 mg/day) significantly increased circulating PCSK9 levels by 34% compared with baseline and placebo and decreased LDL-C levels by 42%. These results suggest that the addition of a PCSK9 inhibitor to statin therapy may result in even further LDL-C decreases.

Urorectal septum malformation sequence: prenatal progression, clinical report, and embryology review.

The urorectal septum malformation sequence (URSMS) is characterized by severe abnormalities of the urorectal septum (URS) and urogenital organs. The primary defect in this condition appears to be a deficiency in caudal mesoderm leading to the malformation of the URS and other structures in the pelvic region. Recent clinical reports discuss prental findings of URSMS [Lubusky et al. (2006); Prenatal Diagnosis 26: 345-349]. However, here we present a case of URSMS with prenatal findings not previously described, review the literature on URSMS, and summarize current embryological understanding of the pathology seen in hindgut development. The unique prenatal finding in the patient was an abdominally located cystic mass that was first seen at 18 weeks of gestation. Over the next 6 weeks, the mass decreased in size until it disappeared. Concurrent with reduction of the cyst, ascites developed. The patient displayed several traditional URSMS indicators including abnormal bladder and dysplastic kidneys. Our findings give additional insight into the embryology of urorectogenital development. Specifically, they suggest that the cystic mass may have been a persistent urachus prior to septation of the cloaca. Postnatal evaluation confirmed a URSMS diagnosis; the newborn had ambiguous genitalia, hypoplastic kidneys, absent uterus, imperforate anus, smooth perineum, and overall underdeveloped urogenital structures.

Serum proprotein convertase subtilisin kexin type 9 is correlated directly with serum LDL cholesterol.

BACKGROUND: Proprotein convertase subtilisin kexin type 9 (PCSK9) is gaining attention as a key regulator of serum LDL-cholesterol (LDLC). This novel serine protease causes the degradation of hepatic LDL receptors by an unknown mechanism. In humans, gain-of-function mutations in the PCSK9 gene cause a form of familial hypercholesterolemia, whereas loss-of-function mutations result in significantly decreased LDLC and decreased cardiovascular risk. Relatively little is known about PCSK9 in human serum. METHODS: We used recombinant human PCSK9 protein and 2 different anti-PCSK9 monoclonal antibodies to build a sandwich ELISA. We measured PCSK9 and lipids in 55 human serum samples and correlated the results. We used the anti-PCSK9 antibodies to assay lipoprotein particle fractions separated by sequential flotation ultracentrifugation. RESULTS: Serum concentrations of PCSK9 ranged from 11 to 115 microg/L and were directly correlated with serum concentrations of LDLC (r = 0.45, P = 0.001) and total cholesterol (r = 0.50, P = 0.0003), but not with triglycerides (r = 0.15, P = 0.28) or HDL cholesterol concentrations (r = 0.13, P = 0.36). PCSK9 was not detectable in any lipoprotein particle fraction, including LDL. CONCLUSIONS: PCSK9 is present in human serum, likely not associated with specific lipoprotein particles. The circulating concentrations of human PCSK9 are directly correlated with LDL and total cholesterol concentrations.