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Context. The impulsive phase of solar flares is a time of rapid energy deposition and heating in the lower solar atmosphere, leading to changes in the temperature and density structure of the region. Aims. We use an Ov density diagnostic formed from the λ192/λ248 line ratio, provided by the Hinode/EIS instrument, to determine the density of flare footpoint plasma at Ov formation temperatures of ~2.5×105 K, giving a constraint on the properties of the heated transition region. Methods. Hinode/EIS rasters from 2 small flare events in December 2007 were used. Raster images were co-aligned to identify and establish the footpoint pixels, multiple-component Gaussian line fitting of the spectra was carried out to isolate the density diagnostic pair, and the density was calculated for several footpoint areas. The assumptions of equilibrium ionisation and optically-thin radiation for the Ov lines used were assessed and found to be acceptable. For one of the events, properties of the electron distribution were deduced from earlier RHESSI hard X-ray observations. These were used to calculate the plasma heating rate delivered by an electron beam for 2 semi-empirical atmospheres under collisional thick-target assumptions. The radiative loss rate for this plasma was also calculated for comparison with possible energy input mechanisms. Results. Electron number densities of up to 1011.9 cm-3 were measured during the flare impulsive phase using the Ov λ192/λ248 diagnostic ratio. The heating rate delivered by an electron beam was found to exceed the radiative losses at this density, corresponding to a height of 450 km, and when assuming a completely ionised target atmosphere far exceed the losses but at a height of 1450-1600 km. A chromospheric thickness of 70-700 km was found to be required to balance a conductive input to the Ov-emitting region with radiative losses. Conclusions. Electron densities have been observed in footpoint sources at transition region temperatures, comparable to previous results but with improved spatial information. The observed densities can be explained by heating of the chromosphere by collisional electrons, with Ov formed at heights of 450-1600 km above the photosphere, depending on the atmospheric ionisation fraction. [ABSTRACT FROM AUTHOR]

Aims. We present direct evidence of the detection of the main energy release site in a non-eruptive solar flare, SOL2013-11-09T06:38 UT. This GOES class C2.6 event was characterised by two flaring ribbons and a compact, bright coronal source located between them, which is the focus of our study. Methods. We use imaging from SDO/AIA, and imaging spectroscopy from RHESSI to characterise the thermal and non-thermal emission from the coronal source, and EUV spectroscopy from the Hinode/Extreme ultraviolet Imaging Spectrometer, which scanned the coronal source during the impulsive peak, to analyse Doppler shifts in Fe xii (log T = 6.2) and Fe xxiv (log T = 7.2) emission lines, and determine the source density. Results. The coronal source exhibited an impulsive emission lightcurve in all SDO/AIA filters during the impulsive phase. RHESSI hard X-ray images indicate both thermal and non-thermal emission at the coronal source, and its plasma temperature derived from RHESSI imaging spectroscopy shows an impulsive rise, reaching a maximum at 12-13 MK about 10 s prior to the hard X-ray peak. High red-shifts associated with this bright source indicate downflows of 40-250 km s-1 at a broad range of temperatures, interpreted as loop shrinkage and/or outflows along the magnetic field. Outflows from the coronal source towards each ribbon are also observed by SDO/AIA images at 171, 193, 211, 304, and 1600 Å. The electron density of the source obtained from a Fe xiv line pair is 1011.50 cm-3 which is collisionally thick to electrons with energy up to 45-65 keV, responsible for the source's non-thermal X-ray emission. Conclusions. Given the rich observational evidence, we conclude that the bright coronal source is the location of the main release of magnetic energy in this flare, with a geometry consistent with component reconnection between crossing, current-carrying loops. We argue that the energy that can be released via reconnection, based on observational estimates, can plausibly account for the non-thermal energetics of the flare. [ABSTRACT FROM AUTHOR]

The temperature distribution of the emitting plasma is a crucial constraint when studying the heating of solar flare footpoints. However, determining this for impulsive phase footpoints has been difficult in the past due to insufficient spatial resolution to resolve the footpoints from the loop structures, and a lack of spectral and temporal coverage. We use the capabilities of Hinode/Extreme Ultraviolet Imaging Spectrometer to obtain the first emission measure distributions (EMDs) from impulsive phase footpoints in six flares. Observations with good spectral coverage were analyzed using a regularized inversion method to recover the EMDs. We find that the EMDs all share a peak temperature of around 8 MK, with lines formed around this temperature having emission measures (EMs) peaking between 1028 and 1029 cm-5, indicating a substantial presence of plasma at very high temperatures within the footpoints. An EMD gradient of EM(T) ~ T is found in all events. Previous theoretical work on EM gradients shows this to be consistent with a scenario in which the deposited flare energy directly heats only the top layer of the flare chromosphere, while deeper layers are heated by conduction. [ABSTRACT FROM AUTHOR]

This article investigates the perspectives of University of Liverpool graduate foundation doctors and their consultants on their preparedness for professional practice. [ABSTRACT FROM AUTHOR]

The article focuses on the findings of a study related to the practice of consultants as well as their experiences in the health care industry in Great Britain. It explores the experiences of newly appointed consultants and investigates the transition from medical student to doctor. Researchers found that new consultants are highly skilled and experienced professionals but may still need a prescriptive support system.

Intravenous administration of quinupristin/dalfopristin outside the hospital setting has not been reported previously. We describe 37 outpatients receiving quinupristin/dalfopristin iv for infections including osteomyelitis, bacteraemia, abscesses and cellulitis. The most frequent aetiological pathogens found were Enterococcus faecium, Staphylococcus aureus and coagulase-negative staphylococci. Patients received an average of 9 days therapy as inpatients and 22 days as outpatients. Quinupristin/dalfopristin was administered using various access devices, most commonly peripherally inserted central catheters and tunnelled central catheters. The bacteriological and clinical success rates were both 89.2%. Five patients were readmitted to hospital; one patient developed catheter-related bacteraemia. The most frequently reported non-venous adverse events were nausea (18.9% of patients), myalgia (18.9%) and arthralgia (13.5%). Sixteen patients experienced venous access-related events, most commonly infusion pain, oedema and phlebitis. In this group of patients, for those who had difficult-to-treat infections, intravenous quinupristin/dalfopristin therapy was generally effective and safe outside the hospital setting. [ABSTRACT FROM AUTHOR]

Context: Knowledge and understanding of gram-negative sepsis have grown over the past 20 years, but the ability to treat severe sepsis successfully has not.Objective: To assess the efficacy and safety of E5 in the treatment of patients with severe gram-negative sepsis.Design: A multicenter, double-blind, randomized, placebo-controlled trial conducted at 136 US medical centers from April 1993 to April 1997, designed with 90% power to detect a 25% relative risk reduction, incorporating 2 planned interim analyses.Setting: Intensive care units at university medical centers, Veterans Affairs medical centers, and community hospitals.Patients: Adults aged 18 years or older, with signs and symptoms consistent with severe sepsis and documented or probable gram-negative infection.Intervention: Patients were assigned to receive 2 doses of either E5, a murine monoclonal antibody directed against endotoxin (n = 550; 2 mg/kg per day by intravenous infusion 24 hours apart) or placebo (n = 552).Main Outcome Measures: The primary end point was mortality at day 14; secondary end points were mortality at day 28, adverse event rates, and 14-day and 28-day mortality in the subgroup without shock at presentation.Results: The trial was stopped after the second interim analysis. A total of 1090 patients received study medication and 915 had gram-negative infection confirmed by culture. There were no statistically significant differences in mortality between the E5 and placebo groups at either day 14 (29.7% vs 31.1%; P = .67) or day 28 (38.5% vs 40.3%; P = .56). Patients presenting without shock had a slightly lower mortality when treated with E5 but the difference was not significant (28.9% vs 33.0% for the E5 and placebo groups, respectively, at day 28; P = .32). There was a similar profile of adverse event rates between E5 and placebo.Conclusions: Despite adequate sample size and high enrollment of patients with confirmed gram-negative sepsis, E5 did not improve short-term survival. Current study rationale and designs should be carefully reviewed before further large-scale studies of patients with sepsis are conducted. [ABSTRACT FROM AUTHOR]

Quinupristin/dalfopristin (Synercid), the first injectable streptogramin antibiotic available for the treatment of complicated gram-positive skin and skin structure infections, was compared with standard comparators (cefazolin, oxacillin or vancomycin) in one USA and one international trial. These two randomized, open-label trials of virtually identical design enrolled a total of 893 patients (450 quinupristin/dalfopristin, 443 comparator). The majority of patients had erysipelas, traumatic wound infection or clean surgical wound infection. Staphylococcus aureus was the most frequently isolated pathogen in both treatment groups and polymicrobial infection was more common in the quinupristin/dalfopristin group than in the comparator group. The clinical success rate (cure plus improvement) in the clinically evaluable population was equivalent between the two treatment groups (68.2% quinupristin/dalfopristin, 70.7% comparator; 95% CI, -10.1, 5.1) despite a shorter mean duration of treatment for quinupristin/dalfopristin patients. In the bacteriologically evaluable population, by-patient and by-pathogen bacteriological eradication rates were somewhat lower for quinupristin/dalfopristin (65.8% and 66.6%, respectively) than for the comparator regimens (72.7% and 77.7%, respectively). The lower bacteriological response rates in the quinupristin/dalfopristin group were, in part, due to a higher rate of polymicrobial infections and a higher incidence of patients classified as clinical failure, a category which included premature discontinuation of treatment because of local venous adverse events. The bacteriological eradication rate for quinupristin/dalfopristin was higher in monomicrobial infections than in polymicrobial infections (72.6% versus 63.3%, respectively), whereas the corresponding rate for the comparator regimens was lower for monomicrobial infections than polymicrobial infections (70.8% versus 83.1%). This finding was not unexpected, since the spectrum of quinupristin/dalfopristin is focused on gram-positive pathogens and additional antibiotics to treat gram-negative bacteria were not required per protocol. The systemic tolerability of both treatment regimens was qualitatively similar. A higher rate of drug-related venous adverse events was reported for quinupristin/dalfopristin (66.2%) than for the comparator regimen (28.4%). Premature discontinuation of study drug was primarily due to adverse clinical events for quinupristin/dalfopristin (19.1%), whereas the most common reason for discontinuation among those receiving the comparator regimens was treatment failure (11.5%). Quinupristin/dalfopristin is an effective alternative for the treatment of hospitalized patients with complicated skin and skin structure infections due to quinupristin/ dalfopristin-susceptible gram-positive organisms, including methicillin- and erythromycin-resistant S. aureus. [ABSTRACT FROM AUTHOR]

The electro-physiological effects of xamoterol were studied in 10 patients with suspected coronary artery disease by intracardiac electro-physiology. Sinoatrial and atrioventricular conduction times were both slightly shortened by 0.1 mg/kg of xamoterol. The atrioventricular nodal refractory periods were shortened without consistent change in atrial refractoriness. This dose raised mean blood pressure by only 3 mmHg and resting heart rate by only 4 bpm. These effects suggest a beta1 agonist activity closer to that of prenalterol than that of pindolol under conditions of rest. [ABSTRACT FROM AUTHOR]

An elderly female presented with persistent upper gastrointestinal bleeding from a mucosal lesion in the second part of the duodenum. This failed to respond to surgery, but was successfully treated with aminocaproic acid. [ABSTRACT FROM PUBLISHER]

Objective: To define the epidemiology and clinical manifestations of hepatitis D virus infection in an institutionalized population.Design: A case-control study of hepatitis B carriers with and without serologic evidence of hepatitis D virus infection. Demographic, institutional, and medical data were obtained through questionnaires and chart review. Clinical status was assessed by liver function assays.Setting: Thirteen Illinois state facilities for the developmentally disabled.Participants: Clients (238) who were hepatitis B carriers.Results: Antibody to hepatitis D virus (anti-HDV) was detected in 71 of 238 (30%) hepatitis B carriers. Nine of thirteen facilities housed positive clients. Previous residence at one facility, designated B, was the strongest correlate of anti-HDV positivity; 85% of positive persons had lived there compared with 16% of negative controls (odds ratio 28.3 [95% CI, 13.2 to 60.7], P less than 0.001). Past hepatitis episodes were more common among anti-HDV-positive clients (37% compared with 7%) (odds ratio, 7.5 [95% CI, 3.0 to 19.1], P less than 0.001) and occurred mainly at facility B from 1950 to 1975. Liver function tests were infrequently abnormal among anti-HDV-positive clients.Conclusions: Results show widespread hepatitis D virus infection in our institutionalized population and suggest that transmission occurred mainly in the past at the overcrowded facility B. The low prevalence of laboratory evidence of chronic liver disease in the anti-HDV-positive clients may be explained by increased mortality among those originally infected from 1950 to 1975. [ABSTRACT FROM AUTHOR]

In a 15-day period, seven patients in a small hospital each had one blood culture positive for Enterobacter cloacae. None of the seven patients was septic. All seven positive culture specimens had been obtained by phlebotomist A, who also had obtained 13 negative culture specimens in the same period. Seven other phlebotomists had drawn 69 blood samples for culture during the same period; none had yielded any microorganism (p = 0.00001). Vials of thrombin, routinely used to coagulate blood specimens for chemical analysis, had been carried on the phlebotomy trays. We observed that phlebotomist A occasionally spilled drops of the viscous thrombin on her finger during the procedures. Culture of the thrombin on her tray yielded E. cloacae. No further cases of E. cloacae bacteremia occurred after she stopped drawing blood for culture and the thrombin on her tray was removed from use. [ABSTRACT FROM AUTHOR]

Presents the response of authors to a letter to the editor about the article "Fibrosing Aiveolitis in Patients With Rheumatoid Arthritis As Assessed by High Resolution Computed Tomography, Chest Radiography, and Pulmonary Function tests," published in the 2001 issue of the journal "Thorax."

Two young women presented with acute bleeding disorders and were subsequently found to have coeliac disease. [ABSTRACT FROM PUBLISHER]

Rates of bacteremia among hospitalized patients with central venous catheters range up to 21%. Few data exist for home intravenous therapy (IVT). We studied 300 patients from two hospital-based home IVT services in 29 months. Diagnoses included 92 cases of osteomyelitis, 33 of pneumonia, 35 of malnutrition, 26 of chronic pain, and 114 of other diseases. Peripheral IVT was given to 97 patients. Mean age was 39.4 years (range, 0.3-98). Hickman, Infuse-A-Port, Broviac, Arrow triple lumen, Hohn, and peripherally inserted central catheters (PICC) were used for a mean of 44 days. Six bacteremias (one death) (2%, 4.6/10,000 catheter days), two subclavian thromboses, 13 catheter site infections, and one additional death occurred. PICC experience included 76 patients, mean age 46 years (range, 4-76), primarily with infections, chronic pain, or dehydration. Mean duration of therapy was 24 days (0-67) and was completed in 51 patients; others completed therapy with standard peripheral catheters a mean of 6 days later. Complications included 17 obstructions by clot, 11 cases of phlebitis, six catheter fractures, five punctures, two accidental removals, and one infiltration. Liquid silicone repaired holes; urokinase opened clots. Successful completion of therapy was more common in the second year, 88% versus 57%. Despite more complications, patients, home IVT nurses, and physicians preferred PICCs. We conclude that home IVT is safe via many means of access, with fewer infections than with hospital care. Such infections may be termed "nosohusial." [ABSTRACT FROM AUTHOR]

Background: Optimizing antimicrobial therapy to attain drug exposure that limits the emergence of resistance, effectively treats the infection, and reduces the risk of side effects is of a particular importance in critically ill patients, in whom normal functions are augmented or/and are infected with pathogens less sensitive to treatment. Achievement of these goals can be enhanced by therapeutic drug monitoring (TDM) for many antibiotics. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method is presented here for simultaneous quantification of ten antimicrobials: cefazolin (CZO), cefepime (CEP), cefotaxime (CTA), ceftazidime (CTZ), ciprofloxacin (CIP), flucloxacillin (FLU), linezolid (LIN), meropenem (MER), piperacillin (PIP) and tazobactam (TAZ) in human plasma., Methods: Plasma samples were precipitated with acetonitrile and injected into the LC-MS/MS. Chromatographic separation was on a Waters Acquity BEH C 18 column. Compounds were eluted with water and acetonitrile containing 0.1 % formic acid, using a gradient (0.5-65 % B), in 3.8 min. The flow rate was 0.4 mL/min, and the run time was 5.8 min., Results: The calibration curves were linear across the tested concentration ranges (0.5-250, CZO, CEP, CTA, CTZ and FLU; 0.2-100, MER and TAZ; 0.1-50, CIP and LIN and 1-500 mg/L, PIP). The intra and inter-day imprecision was < 11 %. Accuracy ranged from 95 to 114 %. CTZ and MER showed ionization suppression while CIP showed ionization enhancement, which was normalized with the use of the internal standard., Conclusion: An LC-MS/MS method for simultaneous quantification of ten antimicrobials in human plasma was developed for routine TDM., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 THE AUTHORS.)

Human immunodeficiency virus (HIV) infection results in a functional impairment of CD4(+) T cells long before a quantitative decline in circulating CD4(+) T cells is evident. The mechanism(s) responsible for this functional unresponsiveness and eventual depletion of CD4(+) T cells remains unclear. Both direct effects of cytopathic infection of CD4(+) cells and indirect effects in which uninfected "bystander" cells are functionally compromised or killed have been implicated as contributing to the immunopathogenesis of HIV infection. Because T-cell receptor engagement of major histocompatibility complex (MHC) molecules in the absence of costimulation mediated via CD28 binding to CD80 (B7-1) or CD86 (B7-2) can lead to anergy or apoptosis, we determined whether HIV type 1 (HIV-1) virions incorporated MHC class I (MHC-I), MHC-II, CD80, or CD86. Microvesicles produced from matched uninfected cells were also evaluated. HIV infection increased MHC-II expression on T- and B-cell lines, macrophages, and peripheral blood mononclear cells (PBMC) but did not significantly alter the expression of CD80 or CD86. HIV virions derived from all MHC-II-positive cell types incorporated high levels of MHC-II, and both virions and microvesicles preferentially incorporated CD86 compared to CD80. CD45, expressed at high levels on cells, was identified as a protein present at high levels on microvesicles but was not detected on HIV-1 virions. Virion-associated, host cell-derived molecules impacted the ability of noninfectious HIV virions to trigger death in freshly isolated PBMC. These results demonstrate the preferential incorporation or exclusion of host cell proteins by budding HIV-1 virions and suggest that host cell proteins present on HIV-1 virions may contribute to the overall pathogenesis of HIV-1 infection.

Recorded cases of asthma have increased in recent years. It is unclear, however, whether this apparent increase in prevalence is accompanied by an increase in severity of the disorder. One potential measure of asthma severity is the requirement for mechanical ventilation. This paper examines those patients ventilated for severe asthma in a district general hospital over a 17 yr period. Since the methods used to assess asthma attacks and the criteria for instituting mechanical ventilation in this hospital did not alter between 1973 and 1992 (Jones criteria), it was possible to compare directly characteristics of all ventilated patients during the study period. The comparison showed that there was a significant increase between the two study periods in the number of patients who required mechanical ventilation. Moreover, in the more recent period both the subjective speed of onset of the asthma attack and the objective time between admission and ventilation were significantly shorter. However, despite this increase in asthma severity the mortality and morbidity in the more recent study period were lower. Overall the results of this study support the view that, in the population served by our district general hospital, asthma has increased in severity. This increased severity is indicated by an increase in the number of patients requiring mechanical ventilation and in the rapidity with which attacks evolved. However, for patients in whom ventilation was required, improved care has lowered both morbidity and mortality.

From 1990 through 1994, we fortuitously isolated Histoplasma capsulatum from six patients with AIDS whose specimens of blood were processed by the BACTEC system using Middlebrook broth selective for acid-fast bacilli (13A medium). Growth indices became positive after an average of 17 days of incubation (range, 11 to 20 days). No acid-fast bacilli were seen, but small budding yeasts characteristic of H. capsulatum were present.

Overwhelming postsplenectomy sepsis is a dreaded sequel of splenectomy. The rate of overwhelming sepsis in children after splenectomy for trauma is reported to be 10 to 30 times that of the general population. Episodes of pneumonia, septicemia, and meningitis in adults after a splenectomy are 166 times more common than in the general population. The care of a patient with burns and asplenia presents many unique management challenges to the burn physician. Awareness of the development of overwhelming postsplenectomy sepsis and its most common infecting organisms is crucial. The specific immunologic deficiencies of reduced immunoglobulin production and cell-mediated immunity that exist in patients after a splenectomy may be compounded by burn injury. Specific treatment recommendations for patients with burns and asplenia are lacking. We report a fatal case of overwhelming sepsis in a patient with asplenia and with an 8% total body surface area partial-thickness burn, and we review the pathogenesis of overwhelming postsplenectomy sepsis. We focus on treatment recommendations regarding the use of prophylactic antimicrobials, intravenous immunoglobulin replacement therapy, and pneumococcal polyvalent vaccine to standardize the care of the patient with burns and asplenia and reduce infectious morbidity and deaths.

We conducted a retrospective review of all cases of postoperative toxic shock syndrome (PTSS) occurring in two community hospitals from 1981-1993, during which time 390,000 surgical procedures were performed. The incidence was 0.003% (12 cases). All wounds in these 12 cases, from those with scant superficial exudates to those with gross purulence, yielded Staphylococcus aureus. All tested isolates were susceptible to methicillin or cephalothin. Patients had a mean maximal temperature of 40 degrees C. All patients had a rash, most in a truncal, "sunburn" pattern. Eleven patients had desquamation. Mean time from surgery to onset of symptoms was 4 days. All patients required vigorous fluid resuscitation. No correlation could be demonstrated between the development of toxic shock syndrome and a patient's age, sex, preoperative skin preparation or administration of antibiotics, members of the surgical team, or duration of procedure. All patients with PTSS survived. PTSS should be considered in the differential diagnosis for the acutely febrile, systemically ill postoperative patient, even when surgical wounds are deceptively benign in appearance. Early recognition and treatment of PTSS is essential for successful outcome.

Purpose: To determine risk factors for postoperative toxic shock syndrome (PTSS), a rare, rapidly progressive, and potentially fatal syndrome associated with postoperative wound infections. Components of PTSS include fever, rash, desquamation, hypotension, and multisystem organ dysfunction., Methods: We conducted a retrospective review of all cases of PTSS occurring in 2 community hospitals from 1981 to 1993, following 390,000 surgical procedures., Results: There were 12 cases of PTSS among the procedures reviewed (0.003%). Orthopedic procedures included excision of accessory navicular and patellar realignment. Wounds ranged from those with scant superficial exudates to those with gross purulence; all cultures yielded Staphylococcus aureus. All tested isolates were susceptible to methicillin or cephalothin. Mean time from surgery to onset of symptoms was 4 days. All patients had sudden onset of fever; mean maximal temperature was 40 degrees C. All patients displayed a rash, most in a truncal "sunburn" pattern. Eleven of 12 patients desquamated. All patients required vigorous fluid resuscitation. All patients survived. No correlation could be demonstrated between PTSS and patient age, sex, preoperative skin preparation or antibiotics, members of surgical team, or duration of procedure., Conclusions: Early recognition and treatment of PTSS are essential. No risk factors for PTSS have been identified. PTSS should be considered in the postoperative, acutely febrile, systemically ill patient, though surgical wounds may be deceptively benign in appearance.

Cold air may worsen asthmatic bronchoconstriction but can lessen breathlessness in normal individuals. Patients with COPD sometimes report improvement in their dyspnea in cold weather. We examined the effect of breathing cold air on exercise tolerance and the perception of breathlessness in 19 patients with stable COPD (age [+/- SD], 63 +/- 6 years; FEV1, 0.99 +/- 0.28 L) in a randomized open study. Patients exercised on a cycle ergometer breathing either room or cold air (-13 degrees C), breathlessness being assessed by Borg scaling. Peak exercise performance improved when breathing cold air (mean +/- SE), 46 +/- 6 W compared with 37 +/- 7 W (p < 0.05) while end-exercise breathlessness fell from 4.6 +/- 0.4 compared with 4.1 +/- 0.5 (p < 0.05) when breathing cold air. End-exercise ETCO2 was higher breathing cold air (6.1 +/- 0.3 kPa compared with 5.5 +/- 0.3 kPa) (p < 0.005). There was no difference in breathlessness at equivalent levels of ventilation. Cold air reduces breathlessness in COPD, probably by inducing relative hypoventilation.