Case report: A novel case of paraneoplastic voltage gated calcium channel antibodies secondary to appendiceal adenocarcinoma.

Voltage gated calcium channels (VGCCs) play a critical role in neural transmission. Antibodies that target these ion channels can disrupt cellular signal transmission resulting in various clinical presentations. VGCC antibodies are most commonly associated with paraneoplastic syndromes such as Lambert-Eatons myasthenic syndrome. Here, we report a 47-year-old female with Stage IV appendiceal adenocarcinoma status post appendectomy and right hemicolectomy, who presented with progressive memory impairment, aphasia, ataxia, weakness, and headache. Neurologic exam was notable for right-sided parietal drift, decreased right arm swing, and ataxia of the bilateral upper extremities, more prominent on the right side. MRI of the brain with and without contrast was unremarkable. Cerebrospinal fluid (CSF) was notable for an elevated myelin basic protein (4.9 ng/mL, normal reference 0.0-3.7 ng/mL) with normal cell count, flow cytometry, and cytology. An extensive serum autoimmune neurology antibody evaluation revealed elevated VGCC autoantibodies (observed value: 96.1 pmol/L, normal range 0.0-30.0 pmol/L). A diagnosis of paraneoplastic voltage gated calcium channel antibodies secondary to appendiceal adenocarcinoma was made. The patient was treated with five exchanges with plasmapheresis over 10 days with significant clinical improvement in her symptoms. Upon literature review, this would be the first reported case of VGCC antibodies associated with appendiceal adenocarcinoma.

Remote ischemic preconditioning for cardioprotection in elective inpatient abdominal surgery - a randomized controlled trial.

BACKGROUND: Perioperative myocardial injury (PMI) is common in elective inpatient abdominal surgery and correlates with mortality risk. Simple measures for reducing PMI in this cohort are needed. This study evaluated whether remote ischemic preconditioning (RIPC) could reduce PMI in elective inpatient abdominal surgery. METHODS: This was a double-blind, sham-controlled trial with 1:1 parallel randomization. PMI was defined as any post-operative serum troponin T (hs-TNT) > 14 ng/L. Eighty-four participants were randomized to receiving RIPC (5 min of upper arm ischemia followed by 5 min reperfusion, for three cycles) or a sham-treatment immediately prior to surgery. The primary outcome was mean peak post-operative troponin in patients with PMI, and secondary outcomes included mean hs-TnT at individual timepoints, post-operative hs-TnT area under the curve (AUC), cardiovascular events and mortality. Predictors of PMI were also collected. Follow up was to 1 year. RESULTS: PMI was observed in 21% of participants. RIPC did not significantly influence the mean peak post-operative hs-TnT concentration in these patients (RIPC 25.65 ng/L [SD 9.33], sham-RIPC 23.91 [SD 13.2], mean difference 1.73 ng/L, 95% confidence interval - 9.7 to 13.1 ng/L, P = 0.753). The treatment did not influence any secondary outcome with the pre-determined definition of PMI. Redefining PMI as > 5 ng/L in line with recent data revealed a non-significant lower incidence in the RIPC cohort (68% vs 81%, P = 0.211), and significantly lower early hs-TnT release (12 h time-point, RIPC 5.5 ng/L [SD 5.5] vs sham 9.1 ng/L [SD 8.2], P = 0.03). CONCLUSIONS: RIPC did not at reduce the incidence or severity of PMI in these general surgical patients using pre-determined definitions. PMI is nonetheless common and effective cardioprotective strategies are required. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov, NCT01850927 , 5th July 2013.

Issues in Estimating Rates of Pediatric Chronic Fatigue Syndrome and Myalgic Encephalomyelitis in a Community-based Sample.

There is a need to examine the prevalence of pediatric chronic fatigue syndrome (CFS) and Myalgic Encephalomyelitis (ME) in the general community, as well as the relative frequency of CFS and ME among various groups (e.g., different age groups, genders, racial/ethnic groups, and socioeconomic strata) and to compare these individuals with community controls. In the present study, we describe an ongoing NIH-funded study, which uses a multiple-stage design, beginning with a brief screening for CFS- and ME-like symptomatology, followed by a more rigorous medical and psychiatric diagnostic evaluation to determine the prevalence of pediatric CFS and ME status in the general community. We provide two case studies showing the types of data we are collecting, and how the data are being used to inform diagnostic decisions.

Through-a-chip partial filling affinity capillary electrophoresis for estimating binding constants of ligands to receptors.

In this paper, we describe the development of a microfluidic/capillary electrophoresis (CE) technique employing partial filling affinity capillary electrophoresis (PFACE) to estimate binding constants of ligands to receptors using as model systems carbonic anhydrase B (CAB, EC 4.2.1.1) and vancomycin from Streptomyces orientalis. Using multilayer soft lithography (MSL), a microfluidic device (MD) consisting of fluid and control channels is fabricated and fitted with an external capillary column. Multiple flow channels allows for manipulation of a zone of ligand and sample containing receptor and non-interacting standards into the MD and subsequently into the capillary column. Upon electrophoresis the sample components migrate into the zone of ligand where equilibrium is established. Changes in migration time of the receptor are used in the analysis to obtain a value for the binding interaction. The manipulation of small volumes of solution on the MD minimizes the need of time-consuming pipetting steps.

Partial-filling affinity capillary electrophoresis techniques to probe the binding of glycopeptide antibiotics to D-Ala-D-Ala terminus peptides.

This work is an overview of our use of affinity capillary electrophoresis (ACE) to estimate binding constants between D-Ala-D-Ala terminus peptides and the glycopeptides vancomycin (Van) from Streptomyces orientalis, teicoplanin (Teic) from Actinoplanes teicomyceticus, and ristocetin A (Rist) from Nocardia lurida. In these studies, modifications in the ACE technique, including partial-filling ACE (PFACE), flow-through PFACE (FTPFACE), on-column ligand derivatization ACE (OCLDACE), on-column receptor derivatization ACE (OCRDACE), multiple-step ligand injection PFACE (MSLIPFACE), and multiple-injection ACE (MIACE), are described and used to determine binding constants of peptides to antibiotics. The findings described herein demonstrate the advantages of ACE in estimating binding parameters between antibiotics and small peptides over other analytical techniques.

Estimation of binding constants between ristocetin and teicoplanin and peptides using on-column ligand derivatization coupled to affinity capillary electrophoresis.

This work utilizes on-column ligand synthesis and affinity capillary electrophoresis (ACE) to determine binding constants ( K(b)) of 9-flourenylmethyloxy carbonyl (Fmoc)-amino acid derivatives to the glycopeptide antibiotics ristocetin (Rist) and teicoplanin (Teic). In this technique, two separate plugs of sample are injected on to the capillary column and electrophoresed. The initial sample plug contains a D-Ala- D-Ala terminus peptide and either one or two non-interacting standard(s). The second plug contains a Fmoc-amino acid- N-hydroxysuccinimide (NHS) ester. The electrophoresis is then carried out with an increasing concentration of Rist or Teic in the running buffer. Upon electrophoresis the initial D-Ala- D-Ala peptide reacts with the Fmoc-amino acid yielding a new Fmoc-amino acid- D-Ala- D-Ala peptide derivative. Continued electrophoresis results in the binding of Rist or Teic to the Fmoc-amino acid- D-Ala- D-Ala peptide derivatives. Analysis of the change in the relative migration time ratio ( RMTR) or electrophoretic mobility (mu) of the Fmoc-amino acid- D-Ala- D-Ala peptide derivatives relative to the non-interacting standards, as a function of the concentration of Rist and Teic, yields a value for K(b). These findings demonstrate the advantage of coupling on-column ligand synthesis to ACE for estimating binding parameters between antibiotics and ligands.