Metastatic Renal Cell Carcinoma of the Head and Neck: A Case Series.

Background: Renal cell carcinoma (RCC) accounts for over 80% of malignant tumors arising from the kidney. However, metastatic RCC to the head and neck is a relatively rare entity. Case Presentation: We describe three patients with metastatic RCC to the head and neck with the involvement of the parapharyngeal space, the level V region of the neck, and the maxillary sinus. Conclusion: Metastatic RCC in the head and neck is uncommon; however, it must be taken into consideration given a patient with a history of RCC. Multiple pathways allow for the spread of RCC to the head and neck region. Treatment options include mastectomy or local radiation and systemic chemotherapy.

Facelift Techniques That Restore Facial Volume.

The aging face results in increase in laxity of the skin and the underlying supporting tissue. There is a fundamental volume loss in the face and it is most apparent in the midface. A traditional superficial musculoaponeurotic system (SMAS) rhytidectomy addresses the laxity of the face but not volume loss. Multivector high SMAS plication allows for natural excess tissue to be placed into the area of volume loss, thereby addressing midface volume loss. This technique is easy to perform, reproducible, and effective with the added benefit of helping to volumize the lower face.

Discovery, Synthesis, and Functional Characterization of a Novel Neuroprotective Natural Product from the Fruit of Alpinia oxyphylla for use in Parkinson's Disease Through LC/MS-Based Multivariate Data Analysis-Guided Fractionation.

Herein we report the discovery of a novel lead compound, oxyphylla A [(R)-4-(2-hydroxy-5-methylphenyl)-5-methylhexanoic acid] (from the fruit of Alpinia oxyphylla), which functions as a neuroprotective agent against Parkinson's disease. To identify a shortlist of candidates from the extract of A. oxyphylla, we employed an integrated strategy combining liquid chromatography/mass spectrometry, bioactivity-guided fractionation, and chemometric analysis. The neuroprotective effects of the shortlisted candidates were validated prior to scaling up the finalized list of potential neuroprotective constituents for more detailed chemical and biological characterization. Oxyphylla A has promising neuroprotective effects: (i) it ameliorates in vitro chemical-induced primary neuronal cell damage and (ii) alleviates chemical-induced dopaminergic neuron loss and behavioral impairment in both zebrafish and mice in vivo. Quantitative proteomics analyses of oxyphylla A-treated primary cerebellar granule neurons that had been intoxicated with 1-methyl-4-phenylpyridinium revealed that oxyphylla A activates nuclear factor-erythroid 2-related factor 2 (NRF2)-a master redox switch-and triggers a cascade of antioxidative responses. These observations were verified independently through western blot analyses. Our integrated metabolomics, chemometrics, and pharmacological strategy led to the efficient discovery of novel bioactive ingredients from A. oxyphylla while avoiding the nontargeting, labor-intensive steps usually required for identification of bioactive compounds. Our successful development of a synthetic route toward oxyphylla A should lead to its availability on a large scale for further functional development and pathological studies.

Online coupling of hydrophilic interaction/strong cation exchange/reversed-phase liquid chromatography with porous graphitic carbon liquid chromatography for simultaneous proteomics and N-glycomics analysis.

In this study we developed a fully automated three-dimensional (3D) liquid chromatography methodology-comprising hydrophilic interaction separation as the first dimension, strong cation exchange fractionation as the second dimension, and low-pH reversed-phase (RP) separation as the third dimension-in conjunction downstream with additional complementary porous graphitic carbon separation, to capture non-retained hydrophilic analytes, for both shotgun proteomics and N-glycomics analyses. The performance of the 3D system alone was benchmarked through the analysis of the total lysate of Saccharomyces cerevisiae, leading to improved hydrophilic peptide coverage, from which we identified 19% and 24% more proteins and peptides, respectively, relative to those identified from a two-dimensional hydrophilic interaction liquid chromatography and low-pH RP chromatography (HILIC-RP) system over the same mass spectrometric acquisition time; consequently, the 3D platform also provided enhanced proteome and protein coverage. When we applied the integrated technology to analyses of the total lysate of primary cerebellar granule neurons, we characterized a total of 2201 proteins and 16,937 unique peptides for this primary cell line, providing one of its most comprehensive datasets. Our new integrated technology also exhibited excellent performance in the first N-glycomics analysis of cynomolgus monkey plasma; we successfully identified 122 proposed N-glycans and 135 N-glycosylation sites from 122 N-glycoproteins, and confirmed the presence of 38 N-glycolylneuraminic acid-containing N-glycans, a rare occurrence in human plasma, through tandem mass spectrometry for the first time.

A versatile reversed phase-strong cation exchange-reversed phase (RP-SCX-RP) multidimensional liquid chromatography platform for qualitative and quantitative shotgun proteomics.

An automatable, robust, high-performance online multidimensional liquid chromatography (MDLC) platform comprising of pH 10 reversed-phase (RP), strong cation exchange (SCX), and pH 2 RP separation stages has been integrated into a modified commercial off-the-shelf LC instrument with a simple rewiring, enabling accelerated routine qualitative and quantitative proteomics analyses. This system has been redesigned with a dual-trap column configuration to improve the throughput by greatly decreasing the system idle time. The performance of this new design has been benchmarked through analysis of the total lysate of S. cerevisiae, in comparison with that of the former tailor-made system featuring more complicated components; the total run time per "load-and-go" LC/MS analysis was approximately 24 h, with minimal idle time and no labor-intensive steps. This platform features high-resolution fractionations, ease of use and a high degree of user programmability in the first two chromatographic dimensions, allowing flexible and effective sampling with (RP-SCX-RP) or without (RP-RP) the inclusion of SCX sub-fractionation; good proteome coverage and reproducibility was demonstrated through the analyses of bacterial, cell culture, and monkey brain tissue proteomes. The viability of the 3D RP-SCX-RP has been proven in proteome-wide studies of STO fibroblasts and yeast tryptic digests, resulting in extended proteome and protein coverages with high reproducibility-in particular, discovering extra-hydrophilic peptides-at the expense of the acquisition time. The identified inventory of the rat pheochromocytoma PC12 cell proteome-a total of 6345 proteins and 97 309 unique peptides is the most comprehensive dataset to date-provides an example of the value of the 3D RP-SCX-RP. The use of orthogonal chromatographic dimensions in the 3D RP-SCX-RP also circumvents the issues of isobaric interference of mass-tagging background contaminations, while significantly improving the accuracy of isobaric tags for relative and absolute quantitation (iTRAQ)-based protein quantitation experiments.

Fully automatable two-dimensional hydrophilic interaction liquid chromatography-reversed phase liquid chromatography with online tandem mass spectrometry for shotgun proteomics.

We have developed a fully automatable two-dimensional liquid chromatography platform for shotgun proteomics analyses based on the online coupling of hydrophilic interaction liquid chromatography (HILIC) - using a nonionic type of TSKgel Amide 80 at either pH 6.8 (neutral) or 2.7 (acidic) - with conventional low-pH reversed-phase chromatography. Online coupling of the neutral-pH HILIC and reversed phase chromatography systems outperformed the acidic HILIC-reversed phase chromatography combination, resulting in 18.4% (1914 versus 1617 nonredundant proteins) and 41.6% (12,989 versus 9172 unique peptides) increases in the number of identified peptides and proteins from duplicate analyses of Rat pheochromocytoma lysates. Armed with this optimized HILIC-reversed phase liquid chromatography platform, we identified 2554 nonredundant proteins from duplicate analyses of a Saccharomyces cerevisiae lysate, with the detected protein abundances spanning from approximately 41 to 10(6) copies per cell, which contained up to approximately 2092 different validated protein species with a dynamic range of concentrations of up to approximately 10(4) . This present study establishes a fully automated platform as a promising methodology to enable online coupling of different hydrophilic HILIC and reversed phase chromatography systems, thereby expanding the repertoire of multidimensional liquid chromatography for shotgun proteomics.

Oseltamivir, an influenza neuraminidase inhibitor drug, does not affect the steady-state pharmacokinetic characteristics of cyclosporine, mycophenolate, or tacrolimus in adult renal transplant patients.

BACKGROUND: An influenza neuraminidase inhibitor drug, oseltamivir (Os) may be prescribed to renal transplant patients to prevent and treat influenza A and B illness. A pharmacokinetic (PK) interaction between Os and immunosuppressive drugs might adversely affect the efficacy and/or toxicity of the latter agents. This study was conducted to determine whether adverse symptoms and acute drug interactions occur during their coadministration. MATERIALS AND METHODS: A randomized, crossover study design was utilized to study the effect of a 75-mg dose of Os on the steady-state PK of cyclosporine A (CyA), mycophenolate mofetil, or tacrolimus (Tac) in a convenience sample of 19 adults with a renal allograft by measurement of total plasma or blood drug concentrations (C(p)) over one 12-hour dose interval. Os PK parameters were determined from its concentrations and those of its metabolite, Os carboxylate, in plasma and urine over 48 hours. RESULTS: Of 19 volunteers, 12 were men, with age (mean ± SD) 46 ± 11 years, weight 83 ± 19 kg, and calculated Cl(creatinine) 64 ± 27 mL/min. Adverse effects were minor and transient. Os did not affect the steady-state C(max), T(max), or area under the concentration versus time curve (AUC) over a 12-hour dose interval of CyA, mycophenolic acid, or Tac or the C(trough) of CyA or mycophenolate but increased the mean C(trough) of Tac by 13%. DISCUSSION: The increase in Tac mean C(trough) during coadministration with Os is not likely clinically important. Os and Os carboxylate PK were similar to those in subjects with native kidneys and similar renal function who have been described in the literature. CONCLUSIONS: These data from a single Os dose study suggest that coadministration is not expected to cause adverse symptoms nor alter the steady-state PK of CyA, mycophenolate mofetil, or Tac in stable adult renal transplant patients with mild renal insufficiency. The data enable a multiple-dose study that reflects clinical practice during influenza exposure and assesses the possibility that chronic exposure to Os might result in a different outcome.

An information-theoretic approach to motor action decoding with a reconfigurable parallel architecture.

Methods for decoding movements from neural spike counts using adaptive filters often rely on minimizing the mean-squared error. However, for non-Gaussian distribution of errors, this approach is not optimal for performance. Therefore, rather than using probabilistic modeling, we propose an alternate non-parametric approach. In order to extract more structure from the input signal (neuronal spike counts) we propose using minimum error entropy (MEE), an information-theoretic approach that minimizes the error entropy as part of an iterative cost function. However, the disadvantage of using MEE as the cost function for adaptive filters is the increase in computational complexity. In this paper we present a comparison between the decoding performance of the analytic Wiener filter and a linear filter trained with MEE, which is then mapped to a parallel architecture in reconfigurable hardware tailored to the computational needs of the MEE filter. We observe considerable speedup from the hardware design. The adaptation of filter weights for the multiple-input, multiple-output linear filters, necessary in motor decoding, is a highly parallelizable algorithm. It can be decomposed into many independent computational blocks with a parallel architecture readily mapped to a field-programmable gate array (FPGA) and scales to large numbers of neurons. By pipelining and parallelizing independent computations in the algorithm, the proposed parallel architecture has sublinear increases in execution time with respect to both window size and filter order.

Ventricular access device versus ventriculosubgaleal shunt in post hemorrhagic hydrocephalus associated with prematurity.

OBJECTIVE: Post-hemorrhagic hydrocephalus (PHH) secondary to germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) continues to be a common problem affecting preterm neonates. Two different devices are used to treat hydrocephalus in preterm neonates under 2.5 kg: (1) ventricular access device (VAD) and (2) ventricular to subgaleal shunt (VSGS). We aim to determine the differences between VAD and VSGS in daily patient management and shunt requirement outcome in premature infants with PHH. METHOD: The medical records of 32 preterm neonates diagnosed with GMH-IVH with PHH treated with a VAD or VSGS were reviewed. The grade of GMH-IVH, need for CSF taps, complications, malfunctions, and need for permanent VP shunt placement were compared between VAD and VSGS groups. RESULTS: All (16/16) VAD patients required daily taps while 4/16 VSGS patients required daily taps. The VAD group had one complication while the VSGS group had five complications. About 28.57% of the patients treated with a VSGS did not require a permanent VP shunt. Around 6.25% of the patients treated with a VAD did not require a permanent VP shunt. CONCLUSION: VSGS is an effective means of providing temporary continuous drainage of CSF in PHH with an acceptable complication rate. VSGS has many advantages that make it superior to VAD as a temporizing shunt.

Management of nevus sebaceous and the risk of Basal cell carcinoma: an 18-year review.

Nevus sebaceous (NS) is a common congenital hamartoma of the skin, usually found on the head and neck. It may undergo malignant transformation to basal cell carcinoma (BCC). However the incidence and lifetime risk of malignant transformation is unknown. We performed an 18-year review of all NS excisions at our institution, to report the number of cases of BCC and other neoplasms within excised NS. The aim is to inform physicians who must weigh the risks in recommending excision of a NS in a pediatric patient population with the risk of malignancy. After a database query for years 1990-2008, charts were reviewed and data were extracted on demographics and surgical history relating to NS. Thirty-one NS with abnormal findings were reviewed microscopically by a dermatopathologist. There were 651 NS distinct lesions among 631 patients and 690 excisions. Twenty-one intralesional diagnoses were found in 18 patients. Five patients (0.8%) had BCC (mean age 12.5 yrs, range 9.7-17.4 yrs). Seven (1.1%) had syringocystadenoma papilliferum (SP) (mean age 8.8 yrs, range 1.7-16.9 yrs), a lesion that may undergo malignant transformation. Malignant transformation of NS can occur in childhood or adolescence. We believe all NS should be excised, however timing of excision can be flexible. Our data do not support age cutoffs or morphologic changes to determine optimal excision time. In conjunction with the treating physician, the parent and patient may weigh the small risk of malignant transformation of NS against the morbidity associated with excision and anesthesia.

Society spotlight: Spotlight on the calibration and validation group.

The Calibration and Validation Group (CVG) was founded in early 1995 by Herman Lam, Chung Chow Chan and YC Lee in Toronto, Canada. At that time, the requirements and the practices of method validation, analytical system qualification and instrument performance verification were only discussed individually among a very small group of professionals; the founders realized that there was a need to form a scientific organization to focus on those subjects and share the learning. Initially, the membership was mainly derived from the regulated pharmaceutical industry, but the participation has grown over the years to include scientists from a wide range of backgrounds, including pharmaceuticals, chemicals, environmental, food, distilleries, biotechnology, instrument vendors, government agencies, local colleges and universities. CVG was officially incorporated as a nonprofit organization in Canada in 1999.

Quantitation of film coating on Zantac 75 mg tablets and Epivir HBV 100 mg tablets by ICP-AES.

PURPOSE: To present a selective analytical Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) method developed and validated for the quantitation of tablet film coatings containing titanium. METHODS: Tablet samples were decomposed by either digestion or dry ashing. The amount of film tablet coating was calculated based on titanium content of the sample. RESULTS: The reported ICP-AES method was accurate, precise, sensitive and linear for determination of titanium concentrations from 2.9 to 8.6 ppm. CONCLUSION: This method provides an accurate determination of the amount of coating on a tablet and has general applicability for a variety of coating formulations containing different elements.