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Background: Ectopic thyroid tissue is a rare abnormality that mainly occurs in the midline of the neck but also in other unusual locations. Because fine needle aspiration biopsy (FNAB) is a widely used procedure for evaluating head and neck and other palpable masses, sampling of these lesions may be encountered., Case: A 66-year-old woman presented with left lateral chest wall mass during follow-up for chronic obstructive pulmonary disease, hypertension and diabetes mellitus. Initial evaluation by FNAB suggested ectopic thyroid tissue, which was confirmed later by tissue biopsy and immunostains. This is the first reported case of ectopic thyroid tissue in the lateral chest wall area., Conclusion: Awareness of this abnormality and the possibility of ectopic thyroid tissue in erratic locations will help cytopathologists make the correct interpretation on FNAB sampling.

Unlabelled: Chondroblastic osteosarcoma accounts for about 25% of all cases of osteosarcoma, which is the most common primary malignancy of the skeleton. Currently, only a few cases of chondroblastic osteosarcoma have been reported to involve the bones of the foot. In this report, we describe the previously unreported occurrence of chondroblastic osteosarcoma involving the left tarsal cuboid in a 15-year-old male. Histologically, the tumor showed an unusually extensive osteoclastic giant cell reaction that initially led to an erroneous diagnosis of giant cell tumor of bone. Because treatment and prognosis are very different for chondroblastic osteosarcoma as compared to giant cell tumor of bone, it is important to make the distinction between these 2 different bone tumors. In this report, we wish to draw attention to occurrence of chondroblastic osteosarcoma in the small bones of the foot, and to the possibility of an extensive giant cell reaction making accurate diagnosis difficult. We also provide a comprehensive review of the literature related to chondroblastic osteosarcoma., Level of Clinical Evidence: 4.

Analyses of ecological and evolutionary processes that shape microbial consortia are facilitated by comprehensive studies of ecosystems with low species richness. In the current study we evaluated the role of recombination in altering the fitness of chemoautotrophic bacteria in their natural environment. Proteomics-inferred genome typing (PIGT) was used to genotype the dominant Leptospirillum group II populations in 27 biofilms sampled from six locations in the Richmond Mine acid mine drainage system (Iron Mountain, CA) over a 4-year period. We observed six distinct genotypes that are recombinants comprised of segments from two 'parental' genotypes. Community genomic analyses revealed additional low abundance recombinant variants. The dominance of some genotypes despite a larger available genome pool, and patterns of spatiotemporal distribution within the ecosystem, indicate selection for distinct recombinants. Genes involved in motility, signal transduction and transport were over-represented in the tens to hundreds of kilobase recombinant blocks, whereas core metabolic functions were significantly under-represented. Our findings demonstrate the power of PIGT and reveal that recombination is a mechanism for fine-scale adaptation in this system.

Objective: Demonstrate the benefits of a multidisciplinary pediatric airway team prepared to evaluate and treat otolaryngology patients with flexible bronchoscopy., Design: Case series., Setting: Tertiary, academic children's hospital., Patients: 10 children (5 male, 5 female age range 2 months-16 years) presenting with complex symptoms potentially referable to large airways., Intervention: Flexible bronchoscopy for diagnostic (bronchoalveolar lavage, ciliary biopsy, assess ongoing surgical intervention, and rule in or rule out foreign body; N=6) or therapeutic (evacuate bronchial mucus plug, laser subglottis when patient has fused cervical spine, and distal instillation [fibrin glue for bronchopleural fistula and dornase alpha for plastic bronchitis]; N=4)., Main Outcome Measure: Retrospectively ask if flexible bronchoscopy and interdisciplinary management improved patient care in these select otolaryngology cases., Results: 10/10 patients benefited from interdisciplinary management including flexible bronchoscopy., Conclusion: Our experience illustrates many uses for flexible bronchoscopy in otolaryngology patients, and suggests that an airway team prepared to use flexible bronchoscopy will create opportunities for improved patient care.

Using agarose gel electrophoresis, we measured the effectiveness of high-Z metal particles of different sizes on SSB and DSB yields for plasmid DNA irradiated with 160 kVp X rays. For plasmid samples prepared in Tris-EDTA buffer, gold nanoparticles were shown to increase G'(SSB) typically by a factor of greater than 2 while G'(DSB) increased by a factor of less than 2. Similar dose-modifying effects were also observed using gold microspheres. Addition of 10(-1) M DMSO typically decreased damage yields by a factor of less than 0.5. Plasmid samples prepared in PBS showed significantly different damage yields compared to those prepared in Tris-EDTA (P < 0.001) with G'(SSB) and G'(DSB) increasing by factors of 100 and 48, respectively. Furthermore, addition of gold nanoparticles to samples prepared in PBS decreased G'(SSB) and G'(DSB) by factors of 0.2 and 0.3, respectively. The results show plasmid damage yields to be highly dependent on differences in particle size between the micro- and nanometer scale, atomic number (Z) of the particle, and scavenging capacity of preparation buffers. This study provides further evidence using a plasmid DNA model system for the potential of high-Z metal nanoparticles as local dose-modifying agents.

Varied Spigelian hernia mesh repair techniques have been described, although evidence suggests laparoscopy results in less morbidity and shorter hospitalization compared with open procedures. Laparoscopic suture repair of Spigelian hernias is rarely reported. Two patients with small Spigelian hernias (< or =2 cm) were diagnosed and repaired laparoscopically using a transabdominal suture technique. Under laparoscopic guidance, a suture-passer was used to place two or three transfacial, interrupted 0 polypropylene sutures along the horizontal plane of the defect. Sutures were tied extracorporeally and closure was confirmed laparoscopically. These cases spurred a review of world literature (2001-2007) including clinical characteristics, operative techniques, and urgency of operations in Spigelian hernia patients. Data were compared using Fisher's exact test. One year postoperatively, the patients are without sequelae or recurrence. Literature review demonstrated most patients were females (P < 0.001), ranged in age from 60 to 80 years (P = 0.042), and presented with left-sided hernias (P = 0.026). Open mesh repair (182/392 cases; 47%) was the most common technique; however, increasingly articles describe laparoscopic mesh repair. Mesh-free laparoscopic suture repair is feasible and safe. This novel uncomplicated approach to small Spigelian hernias combines the benefits of laparoscopic localization, reduction, and closure without the morbidity and cost associated with foreign material.

One of the most promising methods for large-scale studies of protein interactions is isolation of an affinity-tagged protein with its in vivo interaction partners, followed by mass spectrometric identification of the copurified proteins. Previous studies have generated affinity-tagged proteins using genetic tools or cloning systems that are specific to a particular organism. To enable protein-protein interaction studies across a wider range of Gram-negative bacteria, we have developed a methodology based on expression of affinity-tagged "bait" proteins from a medium copy-number plasmid. This construct is based on a broad-host-range vector backbone (pBBR1MCS5). The vector has been modified to incorporate the Gateway DEST vector recombination region, to facilitate cloning and expression of fusion proteins bearing a variety of affinity, fluorescent, or other tags. We demonstrate this methodology by characterizing interactions among subunits of the DNA-dependent RNA polymerase complex in two metabolically versatile Gram-negative microbial species of environmental interest, Rhodopseudomonas palustris CGA010 and Shewanella oneidensis MR-1. Results compared favorably with those for both plasmid and chromosomally encoded affinity-tagged fusion proteins expressed in a model organism, Escherichia coli.

Phytophthora ramorum and Phytophthora sojae are destructive plant pathogens. P. sojae has a narrow host range, whereas P. ramorum has a wide host range. A global proteomics comparison of the vegetative (mycelium) and infective (germinating cyst) life stages of P. sojae and P. ramorum was conducted to identify candidate proteins involved in host range, early infection, and vegetative growth. Sixty-two candidates for early infection, 26 candidates for vegetative growth, and numerous proteins that may be involved in defining host specificity were identified. In addition, common life stage proteomic trends between the organisms were observed. In mycelia, proteins involved in transport and metabolism of amino acids, carbohydrates, and other small molecules were up-regulated. In the germinating cysts, up-regulated proteins associated with lipid transport and metabolism, cytoskeleton, and protein synthesis were observed. It appears that the germinating cyst catabolizes lipid reserves through the beta-oxidation pathway to drive the extensive protein synthesis necessary to produce the germ tube and initiate infection. Once inside the host, the pathogen switches to vegetative growth in which energy is derived from glycolysis and utilized for synthesis of amino acids and other molecules that assist survival in the plant tissue.

Objective: To determine comparative differences on rates of acute urinary retention (AUR) and prostate-related surgeries among patients aged > or =65 years treated with dutasteride or finasteride., Methods: For this retrospective analysis, medical/pharmacy claims data from July 1, 2003, to June 30, 2006, were analyzed for enlarged prostate patients aged > or =65 years treated with 5-alpha reductase inhibitors (5ARIs) regardless of alpha-blocker use. Charlson Comorbidity Index, Thomson Medstat Disease Staging, and propensity score matching techniques were used for comparative analysis., Results: A total of 5090 patients met selection criteria. After 1 year of 5ARI therapy, the AUR rate was lower for dutasteride (12%) when compared with finasteride (14.7%) (odds ratio [OR], 0.79; P = .0042). Risks for prostate-related surgeries were also lower among dutasteride-treated patients (3.9% vs 5.1%, respectively; OR, 0.77; P = .03)., Conclusion: Important therapeutic outcome differences exist between dutasteride and finasteride. Patients treated with dutasteride were significantly less likely to experience AUR and prostate-related surgeries than finasteride patients.

Objective: To evaluate the likelihood of alpha-adrenergic antagonist (alpha-blocker) discontinuation in combination with dutasteride or finasteride among patients aged > or =65 years with enlarged prostate., Method: This retrospective analysis used 2003-2006 data representing more than 30 million managed care members. Medical/pharmacy claims were used to select patients, matched 1:1 using propensity scoring. The proportion remaining on alpha-blocker therapy more than 12 months and time to discontinuation were compared between groups, controlling for covariates using survival analysis., Results: The matched sample included 1674 patients. Alpha-blocker therapy discontinuation was observed at 90 days (86.9% dutasteride patients and 91.8% finasteride patients remained on alpha-blocker therapy). After 12 months, more dutasteride patients discontinued (38.1% remained) alpha-blocker therapy than finasteride patients (56.3% remained)., Conclusions: Patients discontinued alpha-blocker therapy as early as 3 months. Those taking dutasteride were 64% more likely to discontinue alpha-blocker therapy than patients taking finasteride. Dutasteride's impact on discontinuation may have important implications and should be examined further.

Rett Syndrome is associated with decreased peristaltic esophageal waves and gastric dysmotility, resulting in swallowing difficulties and gastric dilation. Rarely, gastric necrosis and perforation occur. Our case represents the third reported case of gastric necrosis and perforation associated with Rett Syndrome. A 31-year-old female after 11 hours of intermittent emesis and constant, sharp abdominal pain presented with evidence of multiorgan system failure including hypovolemic shock, metabolic acidosis, coagulopathy, and hepatorenal failure. A chest radiograph revealed intra-abdominal free air necessitating emergent laparotomy. During exploration, a severely dilated, thin-walled stomach with an area of necrosis and gross perforation was noted. Wedge resection of the necrotic tissue and primary closure were performed. Despite aggressive perioperative resuscitation and ventilation support, the patient died 3 hours postoperatively secondary to refractory shock and hypoxemia. Severe gastric dilation can occur with Rett Syndrome and may cause gastric necrosis and perforation. Prolonged elevated gastric pressures can decrease perfusion and may contribute to perforation. Timely decompression via percutaneous endoscopic or surgical gastrostomy could decrease the risk of perforation particularly when significant gastric distention is present. Consideration of gastric necrosis and perforation in patients with Rett Syndrome may lead to earlier intervention and decreased mortality.

Time-of-flight mass spectrometry was used to investigate fragmentation and energy transfer processes in water by C ions at the distal part of the Bragg peak. Measurements of the positive ion fragments from ionization, electron capture, electron loss, transfer-loss and loss-ionization channels have allowed us for the first time (a) to obtain a quantitative determination of the energy lost by C ions in water and (b) to show that total water fragment ion production has a much flatter profile with projectile energy than would be expected if the water radical formation was assumed to follow the energy-loss profile obtained from available stopping power models.

In September 2004, two consecutive hurricanes (Hurricane Frances and Hurricane Jeanne) made landfall in Stuart, FL, and created healthcare needs that overtaxed the capacity of the local healthcare system. To determine the character and structure of the response to these hurricanes, researchers from the University of New Mexico, Center for Disaster Medicine conducted both a structured written survey of employees and a guided group interview with healthcare system management. The written survey queried staff on topics related to their ability and willingness to get to work and stay at work during the storms. The roundtable interview with leadership resulted in analysis of the preexisting Emergency Operations Plan and its use during the storms, including preparation and execution of plans for staffing, facility operation, communication, community resource utilization, and recovery. In addition, the interaction with federally deployed Disaster Medical Assistance Teams was documented and reviewed. In general, prior planning on the part of the healthcare system in Stuart, FL, resulted in a successful response to both hurricanes. Employees were willing and able to provide the necessary care for patients during the hurricanes, overcoming many physical and emotional barriers that arose during the month-long response. These barriers included concern for the safety of family and pets, inoperable or insufficient communication methods, and damage to employees' personal property and homes. Recommendations for healthcare system preparedness and response were formulated by the researchers based on this healthcare system's successful response to back-to-back hurricanes, including recommendations for interacting with disaster medical resources.

The recent surge in microbial genomic sequencing, combined with the development of high-throughput liquid chromatography-mass-spectrometry-based (LC/LC-MS/MS) proteomics, has raised the question of the extent to which genomic information of one strain or environmental sample can be used to profile proteomes of related strains or samples. Even with decreasing sequencing costs, it remains impractical to obtain genomic sequence for every strain or sample analyzed. Here, we evaluate how shotgun proteomics is affected by amino acid divergence between the sample and the genomic database using a probability-based model and a random mutation simulation model constrained by experimental data. To assess the effects of nonrandom distribution of mutations, we also evaluated identification levels using in silico peptide data from sequenced isolates with average amino acid identities (AAI) varying between 76 and 98%. We compared the predictions to experimental protein identification levels for a sample that was evaluated using a database that included genomic information for the dominant organism and for a closely related variant (95% AAI). The range of models set the boundaries at which half of the proteins in a proteomic experiment can be identified to be 77-92% AAI between orthologs in the sample and database. Consistent with this prediction, experimental data indicated loss of half the identifiable proteins at 90% AAI. Additional analysis indicated a 6.4% reduction of the initial protein coverage per 1% amino acid divergence and total identification loss at 86% AAI. Consequently, shotgun proteomics is capable of cross-strain identifications but avoids most cross-species false positives.

Many bacteria use nonribosomal peptide synthetase (NRPS) proteins to produce peptide antibiotics and siderophores. The catalytic domains of the NRPS proteins are usually linked in large multidomain proteins. Often, additional proteins are coexpressed with NRPS proteins that modify the NRPS peptide products, ensure the availability of substrate building blocks, or play a role in the import or export of the NRPS product. Many NRPS clusters include a small protein of approximately 80 amino acids with homology to the MbtH protein of mycobactin synthesis in Mycobacteria tuberculosis; no function has been assigned to these proteins. Pseudomonas aeruginosa utilizes an NRPS cluster to synthesize the siderophore pyoverdine. The pyoverdine peptide contains a dihydroxyquinoline-based chromophore, as well as two formyl-N-hydroxyornithine residues, which are involved in iron binding. The pyoverdine cluster contains four modular NRPS enzymes and 10-15 additional proteins that are essential for pyoverdine production. Coexpressed with the pyoverdine synthetic enzymes is a 72-amino acid MbtH-like family member designated PA2412. We have determined the three-dimensional structure of the PA2412 protein and describe here the structure and the location of conserved regions. Additionally, we have further analyzed a deletion mutant of the PA2412 protein for growth and pyoverdine production. Our results demonstrate that PA2412 is necessary for the production or secretion of pyoverdine at normal levels. The PA2412 deletion strain is able to use exogenously produced pyoverdine, showing that there is no defect in the uptake or utilization of the iron-pyoverdine complex.

Microbes comprise the majority of extant organisms, yet much remains to be learned about the nature and driving forces of microbial diversification. Our understanding of how microorganisms adapt and evolve can be advanced by genome-wide documentation of the patterns of genetic exchange, particularly if analyses target coexisting members of natural communities. Here we use community genomic data sets to identify, with strain specificity, expressed proteins from the dominant member of a genomically uncharacterized, natural, acidophilic biofilm. Proteomics results reveal a genome shaped by recombination involving chromosomal regions of tens to hundreds of kilobases long that are derived from two closely related bacterial populations. Inter-population genetic exchange was confirmed by multilocus sequence typing of isolates and of uncultivated natural consortia. The findings suggest that exchange of large blocks of gene variants is crucial for the adaptation to specific ecological niches within the very acidic, metal-rich environment. Mass-spectrometry-based discrimination of expressed protein products that differ by as little as a single amino acid enables us to distinguish the behaviour of closely related coexisting organisms. This is important, given that microorganisms grouped together as a single species may have quite distinct roles in natural systems and their interactions might be key to ecosystem optimization. Because proteomic data simultaneously convey information about genome type and activity, strain-resolved community proteomics is an important complement to cultivation-independent genomic (metagenomic) analysis of microorganisms in the natural environment.

Objective: The purpose of this study was to examine the rates of acute urinary retention (AUR) and surgery after initiating 5-alpha reductase inhibitor (5ARI) therapy and to compare the 2 currently available 5ARIs, dutasteride and finasteride, in a real-world, managed care setting. This study constitutes the first direct comparison of therapeutic outcome between a mono 5ARI (finasteride) and a dual 5ARI (dutasteride)., Methods: This is a retrospective descriptive and comparative analysis of the rates of AUR and prostate surgery in patients with benign prostatic hyperplasia (BPH) treated with 5ARI therapy, either dutasteride or finasteride. Data were obtained from the PharMetrics Integrated Medical and Pharmaceutical Database (PIMPD) (Watertown, Mass) during a 6-year period. The PIMPD is a large national healthcare database that represents a total of 85 managed health plans and covers more than 45 million patients. The data analysis included all patients aged 50 years or older diagnosed with BPH who were treated with 5ARIs (dutasteride 0.5 mg/day or finasteride 5 mg/day) for up to 12 months during the 6-year period of January 1, 1999, to March 1, 2005. Patients meeting the selection criteria were evaluated for a total of 12 months with regard to the likelihood of experiencing AUR or prostate-related surgery., Results: After 5 months of 5ARI therapy, the rate of AUR during months 5 to 12 was found to be significantly lower in the dutasteride group compared with the finasteride group (5.3% vs 8.3%). After controlling for background covariates, dutasteride-treated patients were 49.1% less likely to experience AUR than patients treated with finasteride (P = .0207). Patients treated with dutasteride were also less likely to undergo prostate-related surgery, with 1.4% of dutasteride treated patients and 3.4% of patients receiving finasteride undergoing surgery; differences in surgery rates, however, were not statistically significant (P = .0745), even after controlling for background covariates. CONCLUSTION: Although the 2 drugs, dutasteride and finasteride, belong to the same category of 5ARIs, this large retrospective multivariate analysis potentially indicates differences in therapeutic outcomes. In this study, patients treated with dutasteride were less likely to experience AUR and demonstrated a trend toward being less likely to experience surgery than patients treated with finasteride.

Raft and caveolar microdomains have been proposed to participate in numerous cellular functions including signal transduction, cholesterol trafficking, and vesicular sorting. Traditional methods of isolation of rafts from cultured cells and tissue samples have exploited the biochemical properties of these microdomains, i.e., their relative resistance to solubilization by nonionic detergents (at 4 degrees C) and their light buoyant density attributable to their high content of cholesterol and sphingolipids. Thus, a common way to isolate raft microdomains has been their separation on a density gradient in the presence of 0.5-1% Triton X-100 (Bochringer Mannheim Roche Applied Sciences Indianapolis, IN or Sigma-Aldrich, St. Louis, MO). This and other detergent-based methods have been discussed. However, the use of detergents may not be favorable because of artifacts that may arise with their use. (The possibility of rafts solely as detergent-induced artifacts appears to have been diffused by a number of biochemical and biophysical studies that strongly demonstrate the presence of a liquid-ordered phase within biological membranes.) In this chapter, three methods are reviewed to isolate rafts from cultured cells without the use of detergents. Two of these, the sodium carbonate and OptiPrep (Sigma-Aldrich St. Louis, MO) methods, are based on gradient separation and can be used to isolate rafts in general, whereas the third is a magnetic-bead immunoisolation approach and might be used to isolate subpopulations of rafts enriched for different markers such as caveolin-1, flotillin (reggie proteins), or other suitable markers. Together these methods allow for a detergent-free isolation of rafts for biochemical, proteomic, and microscopic studies.

While genome sequencing is becoming ever more routine, genome annotation remains a challenging process. Identification of the coding sequences within the genomic milieu presents a tremendous challenge, especially for eukaryotes with their complex gene architectures. Here, we present a method to assist the annotation process through the use of proteomic data and bioinformatics. Mass spectra of digested protein preparations of the organism of interest were acquired and searched against a protein database created by a six-frame translation of the genome. The identified peptides were mapped back to the genome, compared to the current annotation, and then categorized as supporting or extending the current genome annotation. We named the classified peptides Expressed Peptide Tags (EPTs). The well-annotated bacterium Rhodopseudomonas palustris was used as a control for the method and showed a high degree of correlation between EPT mapping and the current annotation, with 86% of the EPTs confirming existing gene calls and less than 1% of the EPTs expanding on the current annotation. The eukaryotic plant pathogens Phytophthora ramorum and Phytophthora sojae, whose genomes have been recently sequenced and are much less well-annotated, were also subjected to this method. A series of algorithmic steps were taken to increase the confidence of EPT identification for these organisms, including generation of smaller subdatabases to be searched against, and definition of EPT criteria that accommodates the more complex eukaryotic gene architecture. As expected, the analysis of the Phytophthora species showed less correlation between EPT mapping and their current annotation. While approximately 76% of Phytophthora EPTs supported the current annotation, a portion of them (7.7% and 12.9% for P. ramorum and P. sojae, respectively) suggested modification to current gene calls or identified novel genes that were missed by the current genome annotation of these organisms.

Objective: During August of each year, thousands of Nepalese religious pilgrims ascend from 2050 m to 4500 m in 1 to 3 days. Our objectives were to evaluate the incidence of acute mountain sickness (AMS) among this large group of native people, to explore changes in serum electrolytes as subjects ascend to high altitude, and to attempt to determine whether decreased effective circulating volume is associated with the development of AMS., Methods: This was a prospective study with 2 parts. In the first part, demographic, physiologic, and laboratory data were collected from a cohort of 34 pilgrims at both moderate (2050 m) and high altitude (4500 m). Changes that occurred with ascent were compared in subjects who did and did not develop AMS. The second part was a cross sectional study of a different group of 57 pilgrims at the high-altitude site to further determine variables associated with AMS., Results: In the cohort of 34 subjects, Lake Louise score, heart rate, respiratory rate, blood urea nitrogen (BUN), BUN:creatinine ratio, and pH increased at high altitude, whereas oxygen saturation, bicarbonate, creatinine, and PCO2 decreased. Sixteen of these 34 subjects (42%) were diagnosed with AMS; these patients had a statistically significantly lower hematocrit, oxygen saturation, and self-reported water consumption than those without AMS. Of the 57 subjects enrolled in the cross sectional study, 31 (54%) were diagnosed with AMS. These pilgrims had higher heart rates and BUNs than did their non-AMS counterparts., Conclusions: Fifty-two percent of the subjects developed AMS. With ascent to altitude, subjects showed some evidence of decreased effective circulating volume, though there were no clinically significant changes. The data did not show whether decreased circulating volume is a significant risk factor in the development of AMS at high altitude.

We report an automated method for determining charge states from high-resolution mass spectra. Fourier transforms of isotope packets from high-resolution mass spectra are compared to Fourier transforms of modeled isotopic peak packets for a range of charge states. The charge state for the experimental ion packet is determined by the model isotope packet that yields the best match in the comparison of the Fourier transforms. This strategy is demonstrated for determining peptide ion charge states from "zoom scan" data from a linear quadrupole ion trap mass spectrometer, enabling the subsequent automated identification of singly- through quadruply-charged peptide ions, while reducing the numbers of conflicting identifications from ambiguous charge state assignments. We also apply this technique to determine the charges of intact protein ions from LC-FTICR data, demonstrating that it is more sensitive under these experimental conditions than two existing algorithms. The strategy outlined in this paper should be generally applicable to mass spectra obtained from any instrument capable of isotopic resolution.

Objective: Costs of treating the 10 most prevalent diagnosed diseases in men > or = 50 years of age were examined in hopes of identifying areas for better medical management and opportunities to decrease healthcare costs., Methods: A retrospective analysis of a large national managed care database was utilized to assess the costs of treating the 10 most diagnosed diseases in aging men. All men initiating pharmacy treatment between July 1, 1997, and January 31, 2003, for (1) hypertension; (2) coronary artery disease (CAD); (3) type 2 diabetes; (4) enlarged prostate; (5) osteoarthritis; (6) gastroesophageal reflux disease; (7) bursitis; (8) arrhythmias; (9) cataracts; and (10) depression were included. Patients were continuously followed 6 months before and 12 months after initiating treatment. Costs of treatment and likelihood of experiencing a significant event were examined., Results: One-year total disease-specific medical costs were highest for arrhythmias, osteoarthritis, cataracts, and CAD. Total medical costs for bursitis, type 2 diabetes, and enlarged prostate were between $400 and $500. Inpatient costs as a percentage of total medical costs were highest for CAD (75%), osteoarthritis (61%), arrhythmias (57%), and enlarged prostate (40%). For most diseases, pharmacy charges were <50% of the total cost. The likelihood of experiencing a significant clinical event within 1 year of initiating treatment was highest in men with bursitis (23%, surgery) and enlarged prostate (19.2%, acute urinary retention and/or surgery), hypertension (13.5%), and diabetes (9.5%)., Conclusion: The most costly conditions in the 10 most prevalent diseases in men > or = 50 years of age were typically those that required substantial inpatient care. Conditions such as enlarged prostate, diabetes, and hypertension demonstrated a high likelihood of a clinical event within 1 year of initiating treatment. These conditions are therapeutic areas with the greatest likelihood of improvement, given what is known about the use of appropriate pharmacotherapy and the likelihood of treating to goal. Proactive patient management (eg, initiating/maximizing pharmacotherapy) may have the potential to positively impact clinical and economic outcomes for aging men.

As patients continue to take a more active role in their health care, an understanding of patient requests of health care providers, including what happens when requests are not fulfilled, is becoming more important. Although its merits have been debated, direct-to-consumer advertising of prescription drugs generates patient requests. The objective of this study was to assess the influence of physician communication style, respondents' expectations of receiving a requested prescription, and perceived symptom severity on respondents' evaluations of care following a physician denial of a prescription drug request stimulated by direct-to-consumer advertising. A 2 x 2 x 2, between-subjects experimental design was used. The respondents were made up of employees of the University of Mississippi. Physician communication style, respondents' expectations, and respondents' perceived symptom severity were manipulated using vignettes. Respondents' post-visit evaluations of care were assessed by measuring trust in the physician, visit-based satisfaction with the physician, and commitment toward the physician. Factorial analysis of variance procedures for a three-way design were used to test the hypotheses and assess the research questions. Manipulation checks suggested that the independent variables were appropriately manipulated. No significant first-order or second-order interactions were noted in any of the analyses. Post-visit evaluations of care were significantly associated with physician communication style (a partnership response led to better evaluations of care). There were no significant effects of either prior expectation of request fulfillment or perceived symptom severity. However, non-significant trends in mean scores suggested a potential role of these variables in the evaluation process following request denial. The manner in which a physician communicates with an individual is an important determinant of the evaluation of care following the denial of a request. The results suggest that health care providers attempting to minimize the effect of request denials on patient evaluations should make an effort to involve the patient in the decision-making process.

To aid disaster planning, a retrospective review of patients seen by New Mexico 1 Disaster Medical Assistance Team (NM-1 DMAT) after four disasters was conducted. Data analyzed included age, gender, past medical history, chief complaint, diagnosis, diagnostic testing, treatment, triage category, disposition, and time to presentation after the disaster. Data were analyzed for differences between patients presenting early vs. late after a disaster and to test if availability of diagnostic testing changed patient disposition. The results showed that the majority of patients presented with upper respiratory tract infection symptoms, wounds, and musculoskeletal pain. The needs of patients were similar whether they presented early or late. The same proportion of patients was transferred to hospitals when diagnostic testing was available vs. not available, despite a higher level of acuity when diagnostic testing was available. In conclusion, DMATs should be prepared to see high volumes of low acuity patients. Patient needs do not change with time. Diagnostic testing may be useful.

Rhodopseudomonas palustris is a purple nonsulfur anoxygenic phototrophic bacterium that is ubiquitous in soil and water. R. palustris is metabolically versatile with respect to energy generation and carbon and nitrogen metabolism. We have characterized and compared the baseline proteome of a R. palustris wild-type strain grown under six metabolic conditions. The methodology for proteome analysis involved protein fractionation by centrifugation, subsequent digestion with trypsin, and analysis of peptides by liquid chromatography coupled with tandem mass spectrometry. Using these methods, we identified 1664 proteins out of 4836 predicted proteins with conservative filtering constraints. A total of 107 novel hypothetical proteins and 218 conserved hypothetical proteins were detected. Qualitative analyses revealed over 311 proteins exhibiting marked differences between conditions, many of these being hypothetical or conserved hypothetical proteins showing strong correlations with different metabolic modes. For example, five proteins encoded by genes from a novel operon appeared only after anaerobic growth with no evidence of these proteins in extracts of aerobically grown cells. Proteins known to be associated with specialized growth states such as nitrogen fixation, photoautotrophic, or growth on benzoate, were observed to be up-regulated under those states.

There is growing evidence that adherence to the recommended duration of antidepressant therapy results in reduced medical costs compared with nonadherence, and that the likelihood of adhering to therapy is not equivalent across the selective serotonin reuptake inhibitors (SSRIs). As such, the purpose of this study was to assess differences in 6-month medical costs between paroxetine controlled-release (CR) and immediate-release (IR) SSRI agents in a retrospective analysis of patients initiating SSRI therapy identified from the Integrated Healthcare Information Services National Managed Care Benchmark Database during a 2.5-year time frame. Inferential analyses were performed to evaluate differences in 6-month medical costs, controlling for differences in age, sex, utilization of psychiatric specialty care services, titration, pre-period costs, and comorbidity measures. Of the 146 075 patients included in this study, approximately 7% received paroxetine CR. Approximately 29.5% of patients had an anxiety disorder diagnosis; 26.0% had a depression-only diagnosis; and 13.2% had comorbid anxiety and depression. The 6-month medical costs were 244 US dollars lower for patients initiating with paroxetine CR compared with the average medical costs for patients receiving IR SSRIs. Paroxetine CR also had the lowest medical costs compared with each individual SSRI evaluated. After log transformation of costs and adjustment for baseline covariates, the aggregated IR SSRIs were associated with 8.7% higher 6-month medical costs than paroxetine CR (P <.001) and even greater costs after stratifying by diagnosis: 12.5% higher costs in patients with anxiety, 14.3% higher costs in patients with depression, and 15.9% higher costs in patients with comorbid anxiety and depression (P <.001 for all). Each individual IR SSRI was also associated with significantly higher medical costs than paroxetine CR, irrespective of diagnosis. As demonstrated, medical costs over a 6-month time frame were significantly greater for IR SSRIs versus paroxetine CR, even after adjusting for background characteristics and stratifying by diagnosis. Future studies should measure rates of adherence in relation to medical outcomes over an expanded time frame.

Background: Differences in attitudes of patients and physicians toward direct-to-consumer advertising (DTCA) of prescription medications may influence the patient-physician relationship, which may in turn influence health care outcomes., Objective: The objective of this study was to provide empirical evidence to show how the patient-physician relationship may be influenced by DTCA., Methods: The study used a cross-sectional research design. Pharmacists at 71 pharmacies were asked to distribute self-report survey instruments to patients who used either a proton-pump inhibitor or a nonsedating antihistamine by prescription. Data were collected between March and June 2003. Hierarchical multiple regression was used to assess the research propositions., Results: A usable response rate of 7.3% (n=326) was obtained. About 95% of the sample had seen an advertisement for either a proton-pump inhibitor or a nonsedating antihistamine. Response to DTCA was significantly related to the patient's satisfaction with the physician and the patient's evaluation of communication, even after controlling for demographic variables and length of the patient-physician relationship. Other outcome variables (trust, relationship commitment, and average visit time) were not significantly related to DTCA response. Post hoc analyses revealed that DTCA responders, who asked their doctor to prescribe a specific product after seeing its advertisement, rated satisfaction and communication lower than the DTCA nonresponders. Additional follow-up analyses showed that these findings were largely attributed to patients in the proton-pump inhibitor group., Conclusion: The findings suggest that response to DTCA may be significantly related to patients' evaluation of communication quality and their satisfaction with the physician. However, these findings may not generalize to all medical conditions or types of patient. Furthermore, DTCA response does not appear to be related to other patient-physician relationship outcome variables. Given these findings, key variables to explore in future DTCA research with respect to its effect on the patient-physician relationship include patient expectations and disease/condition type.

Effects of the flavonoid rich fraction of the stem bark of Manilkara hexandra (Roxb.) Dubard, have been studied on ethanol, ethanol-indomethacin and pylorus ligated gastric ulcers in experimental animals. Oral administration of the ethyl acetate extract (extract A3) inhibited the formation of gastric lesions induced by ethanol in a dose dependent manner. The protective effect of extract A3 against ethanol induced gastric lesions was not abolished by pretreatment with indomethacin (10 mg kg(-1)). Further, extract A3 inhibited increase in vascular permeability due to ethanol administration. Extent of lipid peroxidation was significantly reduced in animals treated with extract. Extract A3 also inhibited the formation of gastric ulcers induced by pylorus ligation, when administered both orally and intraperitoneally. Moreover, pretreatment with extract A3 increased mucus production and glycoprotein content, which was evident from the rise in mucin activity and TC: PR ratio., (Copyright 2004 John Wiley & Sons, Ltd.)

Objectives/hypothesis: Nontuberculous mycobacterial adenitis of the parotid gland is often difficult to diagnose. The rarity of these infections in the parotid region and the lack of specific guidelines pose a treatment challenge to the clinician. Three cases of nontuberculous mycobacterial adenitis are presented, with clinical response to antibiotics before surgery., Study Design: Retrospective chart review was made of children up to 18 years of age presenting with a parotid mass diagnosed as nontuberculous mycobacterial infection., Methods: Three patients (age range, 15 to 30 mo) with nontuberculous mycobacteria-induced parotid lymphadenitis were treated with a combination antibiotic regimen of clarithromycin and rifabutin or with clarithromycin alone., Results: All three patients responded clinically to the antibiotic treatment as evidenced by a smaller mass size and resolution of the overlying discoloration. Subsequent parotidectomy or biopsy appeared to be easier to perform because of decreased inflammation and edema and a more readily dissectible facial nerve., Conclusion: Children with nontuberculous mycobacteria-induced parotid lymphadenitis should be started on a trial of antibiotic treatment before surgery. Although surgery remains the definitive treatment modality, a larger study of preoperative antibiotic use against nontuberculous mycobacterial adenitis of the parotid in children is necessary.

The present study was designed to investigate the effect of Mimusops elengi (Sapotaceae) against experimental gastric ulcers. The 50% alcoholic extract of Mimusops elengi (Ext E) and its different fractions namely ethyl acetate (Ext E1), n-butanol (Ext E2), methanol (Ext E3) and aqueous (Ext E4) were studied (p.o.) against ethanol-induced gastric damage. Ext E1 was also studied in ethanol-induced, pylorus-ligated and water-immersion plus stress-induced gastric ulcer models. Ranitidine HCl (80 mg kg(-1)) was used as a reference standard. In ethanol-induced gastric ulcer model, pantoprazole (20 mg kg(-1)) was also used as a reference standard. Ext E1 tested in mice up to the dose of 5000 mg kg(-1) (p.o.) did not produce any sign of toxicity. Ext E at the doses of 50, 100, 300 and 500 mg kg(-1) and its different fractions (100 mg kg(-1)) showed reduction in gastric ulceration (P < 0.05). Ext E1 at the doses of 10, 50 and 100 mg kg(-1) showed dose-dependent inhibition of gastric lesions against ethanol-induced gastric damage. In 19 h pylorus-ligated animals, Ext E1 at 50 and 100 mg kg(-1) doses showed significant reduction in ulcer index (P < 0.05). Significant reduction was also observed in total acidity, volume of gastric acid secretion, total acid output and pepsin activity (P < 0.05) when compared with the control group. Besides, Ext E1 showed increase in the mucosal glycoproteins that was evident from significant rise in total carbohydrates to protein ratio (TC:PR ratio) (P < 0.05), which is an indication of mucin activity. Ext E1 also showed protection against water-immersion plus stress-induced gastric lesions that was evident from dose-dependent decrease in ulcer index (P < 0.05), score for intensity (P < 0.05) and total lesion area (P < 0.05) when compared with the control group. It can be concluded from our study that Ext E1 possesses anti-ulcer activity against experimental gastric ulcers. The mechanism of anti-ulcer activity can be attributed to decrease in gastric acid secretory activity along with strengthening of mucosal defensive mechanisms.

A new derivation of continuum distorted-wave theory is presented. It is generalized to magnetically quantized continuum distorted waves. The context is analytic continuation of hydrogenic-state wave functions from below to above threshold, using parabolic coordinates and quantum numbers including m the magnetic quantum number. This continuation applies to excitation, charge transfer, ionization, and double and hybrid events for both light- and heavy-particle collisions. It is applied to the calculation of double-differential cross sections for the single ionization of the hydrogen atom and for a hydrogen molecule by a proton for electrons ejected in the forward direction at a collision energy of 50 keV and 100 keV respectively.

Background: Neoral, a microemulsion formulation of cyclosporine, was approved for use in the United States in 1995. Many studies comparing Neoral and Sandimmune have been conducted, and although most state that Neoral is the superior cyclosporine formulation, results have failed to conclusively demonstrate this claim. The aim of this meta-analysis was to compare the safety and efficacy of Neoral and Sandimmune., Methods: Publications comparing the use of Neoral and Sandimmune were reviewed for demographic variables, adverse events, rejection incidence, graft losses, and serum creatinine. Neoral and Sandimmune were compared in all patients and in the following subgroups: (1) age (adult or pediatric), (2) transplant type (kidney, liver, or heart), (3) indication (de novo or stable), and (4) study design (randomized prospective trials versus nonrandomized, blinded versus open-labeled studies)., Results: The rate of graft loss was similar when comparing Neoral and Sandimmune in all analyses. The incidence of rejection was lower in Neoral-treated de novo renal, liver, and cardiac transplants (P<0.05). There were significantly more adverse events in Sandimmune-treated de novo liver transplants than Neoral-treated de novo liver transplants (P<0.00001). When considering only randomized prospective trials, the incidence of rejection was lower in Neoral-treated de novo and stable patients (P<0.05). However, there were more adverse events in Neoral-treated stable patients (P<0.00001). When considering only blinded studies, there were more adverse events in Neoral-treated patients (P<0.05), whereas in open-labeled studies there was no difference in adverse events comparing Neoral and Sandimmune (P=NS)., Conclusions: Considering all published trials, the data seem to indicate that Neoral therapy is preferred because of a lower rejection incidence, with a trend toward less adverse events. However, when limiting the analysis to only randomized prospective trials, and specifically assessing blinded studies, the data become less clear. Neoral use was associated with more adverse events in blinded studies, and Sandimmune use was associated with more adverse events in open-labeled studies. Careful individual consideration must be given in choosing the best possible cyclosporine formulation.

This paper presents a computer system for analyzing and annotating large-scale genomic sequences. The core of the system is a multiple-gene structure identification program, which predicts the most "probable" gene structures based on the given evidence, including pattern recognition, EST and protein homology information. A graphics-based user interface provides an environment which allows the user to interactively control the evidence to be used in the gene identification process. To overcome the computational bottleneck in the database similarity search used in the gene identification process, we have developed an effective way to partition a database into a set of sub-databases of "related" sequences, and reduced the search problem on a large database to a signature identification problem and a search problem on a much smaller sub-database. This reduces the number of sequences to be searched from N to O ([square root of] N) on average, and hence greatly reduces the search time, where N is the number of sequences in the original database. The system provides the user with the ability to facilitate and modify the analysis and modeling in real time.

A study comparing the relative sensitivity for detecting abnormal stereoacuity in patients with retinal or optic nerve disease on clinically used stereoacuity tests is not available. It is also not apparent from the ophthalmic literature if optic nerve or retinal diseases are likely to have a greater impact on stereoacuity performance. We were also interested in determining a level of visual acuity loss that would likely results in an impairment of stereoacuity on these clinical tests. Forty-two patients with various retinal and optic nerve disorders and eighteen normal subjects were evaluated for stereoacuity using three tests: Titmus Stereoacuity Test (TST), Randot Stereoacuity Test (RST), and TNO Stereoacuity Test (TNO). The performance on these three stereoacuity tests was compared with the normal subjects. Additionally, TST scores from our patients were compared to predicted TST scores derived from a previously published nomogram. For patients with retinal and optic nerve disease, an abnormal score on one clinical test of stereoacuity was likely to predict an abnormality on the other tests. Performance on the TST relative to the predicted value derived from a nomogram was not significantly different for patients with retinal vs. optic nerve disease. With some exceptions, patients with visual acuities of 20/30 or worse in at least one eye were likely to show abnormal stereoacuity.

Several examples of two-step sequential reactions exist where, because of the poor equilibrium conversion by the first reaction, it is desirable to conduct the two reactions simultaneously. In such a scheme, the product of the first reaction is continuously removed by the second reaction, thus not allowing the first reaction to approach chemical equilibrium. Therefore, the first reaction is allowed to proceed in the desired direction at an appreciable rate. However, in many biochemical applications where enzyme catalysts are involved, the enzyme's activities are strong functions of pH. Where the pH optima of the first and second reaction differ by three to four units, the above reaction scheme would be difficult to implement. In these cases, the two reactions can be separated by a thin permeable membrane across which the desired pH gradient is maintained. In this article, it was shown, both by theory and experiment, that a thin, flat membrane of immobilized urease can accomplish this goal when one face of the membrane is exposed to the acidic bulk solution (pH(b) = 4.5) containing a small quantity of urea (0.01 M). In this particular case, the ammonia that was produced in the membrane consumed the incoming hydrogen ions and thus maintained the desired pH gradient. Experimental results indicate that with sufficient urease loading, the face of the membrane opposite to the bulk solution could be maintained at a pH that would allow many enzymes to realize their maximum activities ( approximately 7.5). It was also found that this pH gradient could be maintained even in the presence of a buffer, which greatly enhances the transport of protons into the membrane., ((c) 1993 John Wiley & Sons, Inc.)

Three-dimensional (3-D) reconstructions, by electron microscope tomography, of selectively stained, contrast enhanced Balbiani Ring (BR) hnRNP granules reveal a complex spatial arrangement of RNA-rich domains. This particulate substructure was examined by volume rendering computer graphics. Modeling the arrangement of RNA-rich domains is made difficult by apparent structural flexibility and/or heterogeneity of composition. Formulation of a consensus 3-D arrangement of RNA-rich domains will require an expanded data base of reconstructed BR granules and the development of new image manipulation and analysis techniques. This study demonstrates the potential for ultrastructural cell biology of combining several new techniques: selective nucleic acid staining, electron spectroscopic imaging to enhance contrast, electron microscope tomography and volume rendering computer graphics.

In conclusion, at present, no consistent endocrine abnormalities can be detected in patients suffering from Alzheimer's disease. However, assessment of neuroendocrine function might help identify subpopulations of patients with particular neurotransmission abnormalities who are likely to benefit from a specific pharmacologic strategy. For example, patients in whom cholinomimetic drugs produce the greatest elevation in plasma cortisol concentration appear to derive the most symptomatic benefit from these drugs.