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Introduction Combined chemotherapy and radiotherapy increases long term survival in patients with nasopharyngeal carcinoma. However, radiotherapy of the carotid sinus or brain stem can evolve labile hypertension and orthostatic intolerance from chronic baroreflex failure. Diabetes would also cause this neuropathy. Management of patients with Supine hypertension-Orthostatic hypotension can be very challenging. Methods A case report was done on a 71-year-old man with metastatic nasopharyngeal carcinoma status post radiation therapy who was admitted with severe supine hypertension-orthostatic hypotension. Patient was managed with both non-pharmacological and pharmacological methods, and monitored for postural symptoms, complications of severe supine hypertension—which has been linked to left ventricular hypertrophy and kidney dysfunction, and placed on 24 hour ambulatory blood pressure monitoring to aid in management so as to prevent hypertension induced organ damage. Results This review outlines the pathophysiology of Supine hypertension-Orthostatic hypotension, treatment complications and potential management strategies recommendations for this group of patients. It revealed the benefit of having a 24 hour ambulatory blood pressure monitoring, which provides insight on the timing and magnitude of an individual’s blood pressure fluctuations throughout the day so as to further guide management. Conclusion Chronic baroreflex failure is a late sequela of neck irradiation for naso-pharyngeal carcinoma due to accelerated atherosclerosis in the region of the carotid sinus baroreceptor. Treatment goal is achieved with adequate control of pre-syncopal symptoms and prevention of long term complications. Non-pharmacological interventions remain the first line of therapy, followed by pharmacological interventions as necessary. Nonetheless, management of blood pressure in these elderly patients with baroreflex dysfunction remains challenging and should be individualized. Moving forward, a prospective study on the incidence of late onset, iatrogenic baroreflex failure as a late complication of neck irradiation and its particular relationship to carotid arterial rigidity should be conducted to increase awareness, timely diagnosis and management of the condition among physicians.

Summary Background The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. Methods 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. Findings We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52–88) deaths between 2000 and 2030, of which 37 million (30–48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36–58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52–66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93–150) deaths will be averted by vaccination, of which 58 million (39–76) are due to measles vaccination and 38 million (25–52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59–81) reduction in lifetime mortality in the 2019 birth cohort. Interpretation Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. Funding Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

The pediatric perforated appendix rate is a quality metric measured by the Agency for Healthcare Research and Quality (AHRQ) that reflects access to care. The association of health care utilization prior to presentation with appendicitis is unknown.To determine whether increased health care utilization prior to presentation with appendicitis is associated with lower perforated appendicitis rates in children.Retrospective cohort study of privately insured children drawn from large employer and insurance company administrative data found in the Truven MarketScan national insurance claims database. Cases of appendicitis were identified among 38 348 children 18 years or younger from January 1, 2010, through December 31, 2013, with corresponding primary health care encounters from January 1, 2009, through December 31, 2012. In all, 19 109 eligible children were identified using International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes for appendicitis after excluding those patients who did not have continuous insurance coverage during the study period. Statistical analysis was performed from September 1, 2016, to October 15, 2017.Health care utilization was determined by the number of outpatient clinic encounters for each patient in the 1 to 12 months before presentation with appendicitis.Perforated appendicitis was defined according to the AHRQ by using ICD-9 codes for perforation and hospital length of stay of 3 or more days. Logistic regression models were used for perforated appendicitis after adjustment for age, sex, income, gastrointestinal comorbidities, geographic region, and insurance type.We identified 38 348 children 18 years or younger with ICD-9 diagnosis codes for appendicitis, and 19 109 children remained for analysis after applying exclusion criteria. Of these, 11 422 were boys (59.8%); the mean (SD) age was 12.4 (3.9) years. Of the 19 109 children identified who underwent appendectomy, 5509 (28.8%) presented with perforated appendicitis. Children with perforation had lower outpatient health care utilization in the year before presentation compared with those diagnosed with acute appendicitis (4554 of 5509 children [82.7%] vs 11 937 of 13 600 [87.8%]; P .001). In the adjusted model, outpatient health care utilization before presentation was associated with lower odds of perforated appendicitis (odds ratio [OR], 0.63; 95% CI, 0.58-0.69; P .001). This association increased with visit frequency in the year before presentation (OR, 0.86; 95% CI, 0.77-0.95 for 1-2 visits, P = .003; OR, 0.61; 95% CI, 0.55-0.67 for 3-6 visits, P .001; and OR, 0.43; 95% CI, 0.38-0.48 for ≥7 visits [5-18 years], P .001). Covariates associated with perforation included younger age, geographic region, family income, and higher out-of-pocket insurance plans.Among insured children 18 years or younger, increased health care utilization was associated with lower rates of perforated appendicitis. Primary health care relationships may facilitate timely presentation or serve as a marker for health-related self-efficacy, thereby contributing to outcomes for acute surgical conditions.

Pseudomonas aeruginosa is an opportunistic pathogen that can cause nosocomial and chronic infections in immunocompromised patients. P. aeruginosa secretes a lipoxygenase, LoxA, but the biological role of this enzyme is currently unknown. LoxA is poorly similar in sequence to both soybean LOX-1 (s15-LOX-1) and human 15-LOX-1 (37 and 39%, respectively) yet has kinetics comparably fast versus those of s15-LOX-1 (at pH 6.5, Kcat = 181 ± 6 s(-1) and Kcat/KM = 16 ± 2 μM(-1) s(-1)). LoxA is capable of efficiently catalyzing the peroxidation of a broad range of free fatty acid (FA) substrates (e.g., AA and LA) with high positional specificity, indicating a 15-LOX. Its mechanism includes hydrogen atom abstraction [a kinetic isotope effect (KIE) of >30], yet LoxA is a poor catalyst against phosphoester FAs, suggesting that LoxA is not involved in membrane decomposition. LoxA also does not react with 5- or 15-HETEs, indicating poor involvement in lipoxin production. A LOX high-throughput screen of the LOPAC library yielded a variety of low-micromolar inhibitors; however, none selectively targeted LoxA over the human LOX isozymes. With respect to cellular activity, the level of LoxA expression is increased when P. aeruginosa undergoes the transition to a biofilm mode of growth, but LoxA is not required for biofilm growth on abiotic surfaces. However, LoxA does appear to be required for biofilm growth in association with the host airway epithelium, suggesting a role for LoxA in mediating bacterium-host interactions during colonization.

HER2 (Epidermal Human Growth Factor Receptor), is one of receptors in the epidermal growth factor receptor family. The overexpression of HER2 was determined in 25% to 35% of patients which were positive with breast cancer and in some of different cancers such as ovary cancer, uterus cancer... Due to this characteristic, HER2 has become an effective molecular marker for pre-diagnosis as well as a strike target for immune therapeutically treatment. Currently, there are different types of monoclonal antibodies (mAbs) specific to HER2 which produced based on recombinant DNA technology. These recombinant mAbs are bringing many benefits for diagnosis and making more effective in the treatment of breast cancer. In this research, the pair of primers (BacHER2F/BacHER2R) was designed to amplify antiHER2 antibody (antiHER2 Ab) fragment (Single-chain variable fragment, scFv) which had been moved into a cloning vector and confirmed by sequencing. An expression vector containing this fragment (vector Bacmid/AntiHER2) has been constructed and transfected into a cultured Sf9 insect cells to produce recombinant baculovirus (r-BV). The virus then infected to silkworm Bombyx mori and the recombinant antiHER2 Ab (r-antiHER2 Ab) was expressed successfully. The expressed protein was confirmed by Western blot analysis. We obtained r-antiHER2 Ab using Ni-NTA affinity chromatography. Our result verified that we received purified r-antiHER2 Ab with 95% purity, which can be used for next experiments.

Objective: To characterize national trends in non-fatal BB/pellet gun related injury rates for persons aged 19 years or younger in relation to trends in non-fatal and fatal firearm related injury rates and discuss these trends in light of injury prevention and violence prevention efforts. Setting: The National Electronic Injury Surveillance System (NEISS) includes approximately 100 hospitals with at least six beds that provide emergency services. These hospitals comprise a stratified probability sample of all US hospitals with emergency departments. The National Vital Statistics System (NVSS) is a complete census of all death certificates filed by states and is compiled annually. Methods: National data on BB/pellet gun related injuries and injury rates were examined along with fatal and non-fatal firearm related injuries and injury rates. Non-fatal injury data for all BB/pellet gun related injury cases from 1985 through 1999, and firearm related injury cases from 1993 through 1999 were obtained from hospital emergency department records using the NEISS. Firearm related deaths from 1985 through 1999 were obtained from the NVSS. Results: BB/pellet gun related injury rates increased from age 3 years to a peak at age 13 years and declined thereafter. In contrast, firearm related injury and death rates increased gradually until age 13 and then increased sharply until age 18 years. For persons aged 19 years and younger, BB/pellet gun related injury rates increased from the late 1980s until the early 1990s and then declined until 1999; these injury rates per 100 000 population were 24.0 in 1988, 32.8 in 1992, and 18.3 in 1999. This trend was similar to those for fatal and non-fatal firearm related injury rates per 100 000 which were 4.5 in 1985, 7.8 in 1993, and 4.3 in 1999 (fatal) and 38.6 in 1993 and 16.3 in 1999 (non-fatal). In 1999, an estimated 14 313 (95% confidence interval (CI) 12 025 to 16 601) cases with non-fatal BB/pellet gun injuries and an estimated 12 748 (95% CI 7881–17 615) cases with non-fatal firearm related injuries among persons aged 19 years and younger were treated in US hospital emergency departments. Conclusions: BB/pellet gun related and firearm related injury rates show similar declines since the early 1990s. These declines coincide with a growing number of prevention efforts aimed at reducing injuries to children from unsupervised access to guns and from youth violence. Evaluations at the state and local level are needed to determine true associations.

The aim of this study was to define the epidemiology and clinical manifestations of late recurrent candidemia. For this purpose, late recurrent candidemia was defined as an episode of candidemia occurring at least 1 month after the apparent complete resolution of an infectious episode caused by the same Candida sp. A total of five patients with recurrent candidemia were investigated. For all patients, isolates from the initial and recurrent episodes of candidemia were available for in vitro susceptibility testing and genetic characterization by DNA-based techniques. The results revealed the following salient features: prolonged duration between the initial and recurrent episodes (range, 1-8 months); recurrence of candidemia despite anti-fungal therapy; importance of retained intravascular catheters, neutropenia, and corticosteroids as factors predisposing to recurrence; high morbidity and mortality; no emergence of antifungal drug resistance between the initial and recurrent episodes; and relapse of infection due to the original infecting strain, rather than reinfection with a new strain. These findings raise several issues about the management and follow-up of patients with candidemia, which require assessment in future studies.

We addressed the influence of the incubation time (24 h versus 48 h), starting inoculum size (standard inoculum size, ∼10 3 CFU/ml, versus large inoculum size, ∼10 4 CFU/ml), and supplementation with 2% glucose of RPMI 1640 medium on the spectrophotometric determination of the MICs of amphotericin B, fluconazole, and itraconazole. We compared the MICs determined spectrophotometrically with those determined by the standard broth macrodilution method (National Committee for Clinical Laboratory Standards approved guideline M27-A). The agreement between the results of the spectrophotometric and standard methods for amphotericin B testing was 100%; this agreement was independent of the inoculum size and incubation time. On the other hand, the agreement for the results for fluconazole testing and itraconazole testing was dependent on the inoculum size and incubation time. With large inoculum size, excellent agreement can be achieved at 24 h. With standard inoculum size, acceptable agreement can be achieved only at 48 h. In contrast to previous observations, the addition of 2% glucose did not have any significant impact on the growth density at 24 h, nor did it improve the agreement with the standard method. Furthermore, supplemental glucose might falsely elevate the MIC at 48 h.

We investigated the interaction between amphotericin B and azithromycin in vitro against 26 clinical isolates of Fusarium. Synergy was demonstrated in all isolates. Amphotericin B MICs were reduced from a mean of 1 mg/L when tested alone to a mean of 0.37 mg/L when tested in combination with azithromycin. Azithromycin demonstrated no activity against Fusarium when tested alone (MIC > 128 mg/L). When combined with amphotericin B the mean MIC was reduced to 5.5 mg/L, a level readily achieved in tissue. Given the resistance of Fusarium to conventional therapy, the in-vitro synergy between amphotericin B and azithromycin might prove to be important in therapy for fusariosis.

The diagnosis of a rectovaginal or enterovaginal fistula is mostly made by a careful historical of a faecal vaginal discharge. When a rectovaginal fistula is low, an examination will demonstrate it with ease. However, when there is a high and small fistula into the vault or the fornix of the vagina, traditional methods of small bowel enema and barium enema may not demonstrate the fistula. Ultrasound and magnetic resonance imaging may demonstrate a fistula but not the nature of the bowel involved. Vaginography has been the most successful imaging method to date. Demonstrating an enterovaginal fistula and substantiating whether or not the rectum, the small bowel alone or both are implicated are important for operation planning; a fistulogram through the vagina by endoscopic method is a simple and useful adjunct to the available methods of imaging enterovaginal fistulas. We report a case and discuss a technique of endoscopic fistulography through a small fistulous opening high in the vagina. We believe that this technique is accurate, simple and complementary to vaginography in demonstrating an enterovaginal fistula.

An increasing number of patients older than 65 years are referred for and have access to organ transplantation, and an increasing number of older adults are donating organs. Although short-term outcomes are similar in older versus younger transplant recipients, older donor or recipient age is associated with inferior long-term outcomes. However, age is often a proxy for other factors that might predict poor outcomes more strongly and better identify patients at risk for adverse events. Approaches to transplantation in older adults vary across programs, but despite recent gains in access and the increased use of marginal organs, older patients remain less likely than other groups to receive a transplant, and those who do are highly selected. Moreover, few studies have addressed geriatric issues in transplant patient selection or management, or the implications on health span and disability when patients age to late life with a transplanted organ. This paper summarizes a recent trans-disciplinary workshop held by ASP, in collaboration with NHLBI, NIA, NIAID, NIDDK, and AGS, to address issues related to kidney, liver, lung, or heart transplantation in older adults and to propose a research agenda in these areas.

The (-) enantiomers of 2',3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC] and 2',3'-dideoxy-3'-thiacytidine [(-)-BCH-189] were recently shown to inhibit selectively human immunodeficiency viruses (HIV) and hepatitis B virus in vitro. In the current study, the potential for HIV type 1 (HIV-1) resistance to these compounds was evaluated by serial passage of the virus in human peripheral blood mononuclear cells and MT-2 cells in the presence of increasing drug concentrations. Highly drug-resistant HIV-1 variants dominated the replicating virus population after two or more cycles of infection. The resistant variants were cross-resistant to (-)-FTC, (-)-BCH-189, and their (+) congeners but remained susceptible to 2',3'-dideoxycytidine, 3'-azido-3'-deoxythymidine, 3'-fluoro-3'-deoxythymidine, 2',3'-dideoxyinosine, phosphonoformate, the TIBO compound R82150, and the bis(heteroaryl)piperazine derivative U-87201E. Reverse transcriptase derived from drug-resistant viral particles was 15- to 50-fold less susceptible to the 5'-triphosphates of FTC and BCH-189 compared with enzyme from parental drug-susceptible virus. DNA sequence analysis of the reverse transcriptase gene amplified from resistant viruses consistently identified mutations at codon 184 from Met (ATG) to Val (GTG or GTA) or Ile (ATA). Sequence analysis of amplified reverse transcriptase from a patient who had received (-)-BCH-189 therapy for 4 months demonstrated a mixture of the Met-184-to-Val (GTG) mutation and the parental genotype, indicating that the Met-184 mutation can occur in vivo.

Sequence data on Helicobacter pylori 16S rRNA were used to select two 22-base oligonucleotide primers for use in a polymerase chain reaction (PCR) for detection of H. pylori. H. pylori cells were treated with lysis buffer, boiled, and chloroform extracted. Reverse transcription of rRNA was followed by PCR amplification (RT-PCR) of the synthesized cDNA and 16S rRNA gene. The amplified PCR products were analyzed by agarose gel electrophoresis and Southern blotting. Using ethidium bromide-stained agarose gels, we were able to detect the expected 500-bp DNA fragment from as few as two H. pylori organisms per reaction. The specificity of the RT-PCR assay was tested with 27 clinical isolates and related reference strains; although the number of bacterial cells used per reaction was 10(5)-fold greater than the number of H. pylori organisms used, amplification was detected only with bacteria in the same genus, H. cinaedi and H. mustelae. Ten H. pylori organisms per biopsy specimen were detected on agarose gels when organisms were added to samples prepared from a processed colon biopsy sample. RT-PCR results were consistent with urea breath test and culture results in 14 of 15 gastric biopsy specimens; the specificity was 100%. RT-PCR of rRNA from H. pylori increased the sensitivity of pathogen detection at least 25- to 50-fold compared with that of previous PCR assays. This low level of detection by RT-PCR assay may prove to be well suited for verifying eradication following therapy.

Twenty-nine Aspergillus isolates and 25 Fusarium isolates underwent in vitro antifungal susceptibility testing by a broth macrodilution procedure adapted from the National Committee for Clinical Laboratory Standards guidelines. The MIC50s of both voriconazole and amphotericin B were 0.5 microg/ml and 1 microg/ml against species of Aspergillus and Fusarium, respectively, while the MIC90s of both agents were 1 and 2 microg/ml. Voriconazole was more active in vitro than amphotericin B: the geometric mean MICs of voriconazole and amphotericin B against Aspergillus spp. were 0.36 microg/ml and 0.64 microg/ml, respectively. Voriconazole also demonstrated fungicidal activity against Aspergillus spp., with 86% (24/29) of isolates exhibiting minimum lethal concentrations ofor = 4 microg/ml.

The potential role of azithromycin in combination with amphotericin B against 25 clinical isolates of Aspergillus was assessed. The MIC of amphotericin B was 1 microg/ml for 44% of the isolates, 0.5 microg/ml for 48%, and 0.25 microg/ml for 8%. All isolates were resistant to azithromycin. Synergism, defined as aor = twofold reduction in the MIC of both drugs upon combination, was demonstrated between amphotericin B and azithromycin for all 25 isolates. To prove that azithromycin exerts its antifungal effect by inhibiting protein synthesis, we studied [35S]-methionine incorporation into protein in one Aspergillus isolate. Neither amphotericin B at 0.125 microg/ml (fourfold below its MIC) nor azithromycin at 16 microg/ml (or = 16-fold below its MIC) had any effect on protein synthesis when tested alone. Upon combination, however, a 68% inhibition in protein synthesis was evident by the inhibition of [35S]-methionine incorporation.

We compared the in-vitro activity of fluconazole, itraconazole, ketoconazole and voriconazole against 67 blood isolates of Candida spp. exhibiting a wide range of fluconazole MICs (0.125 to >64 mg/L). Voriconazole was the most potent in vitro, followed by itraconazole, ketoconazole and fluconazole. Itraconazole and voriconazole had in-vitro activity against fluconazole-susceptible and -resistant candida isolates. Higher itraconazole and voriconazole MICs were observed in isolates exhibiting higher fluconazole MICs, suggesting cross-resistance. Itraconazole and voriconazole MICs of > or =16 mg/L were observed only in Candida albicans and Candida tropicalis. Candida krusei and Candida glabrata exhibited itraconazole MICs of 0.5-1 mg/L and voriconazole MICs of 0.25-0.5 mg/L.

This study elucidates the role of combined fluconazole and flucytosine as therapy for cryptococcosis in the murine model of meningitis. Three strains of Cryptococcus neoformans for which the range of fluconazole MICs was wide--2 microg/ml (susceptible strain), 8 microg/ml (moderately susceptible strain), and 32 microg/ml (resistant strain)--were used for infection. One day postinfection, the mice were randomized into eight treatment groups: placebo; flucytosine (40 mg/kg of body weight/day); fluconazole at 3 mg/kg/day (low dosage), 10 mg/kg/day (moderate dosage), or 20 mg/kg/day (high dosage); and combined flucytosine and fluconazole at low, moderate, or high doses of fluconazole. Three major findings were demonstrated: (i) correlation between the MICs for the isolates and the in vivo effectiveness of fluconazole as assessed by the reduction in cryptococcal brain burden, (ii) a dose-response curve (a higher dose of fluconazole was significantly more efficacious than a lower dose [P < 0.001]), and (iii) synergism between fluconazole and flucytosine (therapy with a combination of fluconazole and flucytosine was superior to therapy with either agent alone [P < 0.01]).

Listeria monocytogenes has been increasingly implicated in spontaneous bacterial peritonitis in patients with cirrhosis. This bacterium can be mistaken for diphtheroids and gram-positive cocci if special attention is not paid to the motility pattern and specific biochemical tests. Although the sensitivity of ascitic fluid Gram stain is low, we describe a case in which the Gram stain of the ascites fluid was positive. This issue is now pertinent given recent recommendations of third-generation cephalosporin antibiotics as empiric therapy for spontaneous bacterial peritonitis; Listeria is resistant to cephalosporin agents. A positive Gram stain could affect the empiric antibiotic therapy. We review the clinical presentation and outcome in nine other cases of Listeria peritonitis occurring in cirrhotic patients.

To investigate whether the oral cavity is a potential reservoir and possible sanctuary for Helicobacter pylori, supragingival and subgingival plaques were analyzed by a Helicobacter genus-specific reverse transcriptase-polymerase chain reaction based on the sequence data of H. pylori 16S rRNA. The amplified 500-bp DNA fragment was identified by ethidium bromide staining after agarose gel electrophoresis and by Southern hybridization. Twenty-five dyspeptic patients were studied. Histologic examination of gastric biopsy specimens revealed that 18 had H. pylori gastritis and 7 did not. For seven of the 18 (38.8%) patients with proven H. pylori gastritis, H. pylori was also identified in their dental plaque. None of the patients without H. pylori gastritis had H. pylori in their dental plaque. The detection of H. pylori in dental plaque suggests that this H. pylori colonization is not restricted to the gastric mucosa and that this ecological niche may serve as a possible sanctuary which may be responsible for reinoculation of the stomach after topical anti-H. pylori therapies such as bismuth.

Background: Although much has been written about techniques for making a good stoma, little has been described regarding how to excise a trephine that will perfectly fit a given end stoma. Methods A reproducible technique for making a stomal trephine to a precise fit for each stoma is described. Results: More than 20 stomas have been made with good results. Conclusion: The skin trephine should have a diameter approximately two-thirds of the width of the crushed bowel end.