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1.
Phys Rev Lett ; 129(11): 111101, 2022 Sep 09.
Article in English | MEDLINE | ID: mdl-36154418

ABSTRACT

The central region of the Milky Way is one of the foremost locations to look for dark matter (DM) signatures. We report the first results on a search for DM particle annihilation signals using new observations from an unprecedented γ-ray survey of the Galactic Center (GC) region, i.e., the Inner Galaxy Survey, at very high energies (≳100 GeV) performed with the H.E.S.S. array of five ground-based Cherenkov telescopes. No significant γ-ray excess is found in the search region of the 2014-2020 dataset and a profile likelihood ratio analysis is carried out to set exclusion limits on the annihilation cross section ⟨σv⟩. Assuming Einasto and Navarro-Frenk-White (NFW) DM density profiles at the GC, these constraints are the strongest obtained so far in the TeV DM mass range. For the Einasto profile, the constraints reach ⟨σv⟩ values of 3.7×10^{-26} cm^{3} s^{-1} for 1.5 TeV DM mass in the W^{+}W^{-} annihilation channel, and 1.2×10^{-26} cm^{3} s^{-1} for 0.7 TeV DM mass in the τ^{+}τ^{-} annihilation channel. With the H.E.S.S. Inner Galaxy Survey, ground-based γ-ray observations thus probe ⟨σv⟩ values expected from thermal-relic annihilating TeV DM particles.

2.
Nature ; 523(7562): 568-71, 2015 Jul 30.
Article in English | MEDLINE | ID: mdl-26223623

ABSTRACT

Aurorae are detected from all the magnetized planets in our Solar System, including Earth. They are powered by magnetospheric current systems that lead to the precipitation of energetic electrons into the high-latitude regions of the upper atmosphere. In the case of the gas-giant planets, these aurorae include highly polarized radio emission at kilohertz and megahertz frequencies produced by the precipitating electrons, as well as continuum and line emission in the infrared, optical, ultraviolet and X-ray parts of the spectrum, associated with the collisional excitation and heating of the hydrogen-dominated atmosphere. Here we report simultaneous radio and optical spectroscopic observations of an object at the end of the stellar main sequence, located right at the boundary between stars and brown dwarfs, from which we have detected radio and optical auroral emissions both powered by magnetospheric currents. Whereas the magnetic activity of stars like our Sun is powered by processes that occur in their lower atmospheres, these aurorae are powered by processes originating much further out in the magnetosphere of the dwarf star that couple energy into the lower atmosphere. The dissipated power is at least four orders of magnitude larger than what is produced in the Jovian magnetosphere, revealing aurorae to be a potentially ubiquitous signature of large-scale magnetospheres that can scale to luminosities far greater than those observed in our Solar System. These magnetospheric current systems may also play a part in powering some of the weather phenomena reported on brown dwarfs.

3.
Science ; 383(6681): 402-406, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38271522

ABSTRACT

SS 433 is a microquasar, a stellar binary system that launches collimated relativistic jets. We observed SS 433 in gamma rays using the High Energy Stereoscopic System (H.E.S.S.) and found an energy-dependent shift in the apparent position of the gamma-ray emission from the parsec-scale jets. These observations trace the energetic electron population and indicate that inverse Compton scattering is the emission mechanism of the gamma rays. Our modeling of the energy-dependent gamma-ray morphology constrains the location of particle acceleration and requires an abrupt deceleration of the jet flow. We infer the presence of shocks on either side of the binary system, at distances of 25 to 30 parsecs, and that self-collimation of the precessing jets forms the shocks, which then efficiently accelerate electrons.

4.
Clin Res Cardiol ; 112(7): 901-910, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36656377

ABSTRACT

BACKGROUND: We aimed to study whether improvement in renal function by serelaxin in patients who were hospitalized for acute heart failure (HF) might explain any potential effect on clinical outcomes. METHODS: We included 6318 patients from the RELAXin in AHF-2 (RELAX-AHF2) study. Improvement in renal function was defined as a decrease in serum creatinine of ≥ 0.3 mg/dL and ≥ 25%, or increase in estimated glomerular filtration rate of ≥ 25% between baseline and day 2. Worsening renal function (WRF) was defined as the reverse. We performed causal mediation analyses regarding 180-day all-cause mortality (ACM), cardiovascular death (CVD), and hospitalization for HF/renal failure. RESULTS: Improvement in renal function was more frequently observed with serelaxin when compared with placebo [OR 1.88 (95% CI 1.64-2.15, p < 0.0001)], but was not associated with subsequent clinical outcomes. WRF occurred less frequent with serelaxin [OR 0.70 (95% CI 0.60-0.83, p < 0.0001)] and was associated with increased risk of ACM, worsening HF and the composite of CVD and HF or renal failure hospitalization. Improvement in renal function did not mediate the treatment effect of serelaxin [CVD HR 1.01 (0.99-1.04), ACM HR 1.01 (0.99-1.03), HF/renal failure hospitalization HR 0.99 (0.97-1.00)]. CONCLUSIONS: Despite the significant improvement in renal function by serelaxin in patients with acute HF, the potential beneficial treatment effect was not mediated by improvement in renal function. These data suggest that improvement in renal function might not be a suitable surrogate marker for potential treatment efficacy in future studies with novel relaxin agents in acute HF. Central illustration. Conceptual model explaining mediation analysis; treatment efficacy of heart failure therapies mediated by renal function.


Subject(s)
Heart Failure , Relaxin , Renal Insufficiency , Humans , Acute Disease , Kidney , Recombinant Proteins/pharmacology , Relaxin/pharmacology , Renal Insufficiency/complications , Treatment Outcome , Vasodilator Agents/pharmacology
5.
Science ; 376(6588): 77-80, 2022 04.
Article in English | MEDLINE | ID: mdl-35271303

ABSTRACT

Recurrent novae are repeating thermonuclear explosions in the outer layers of white dwarfs, due to the accretion of fresh material from a binary companion. The shock generated when ejected material slams into the companion star's wind can accelerate particles. We report very-high-energy (VHE; [Formula: see text]) gamma rays from the recurrent nova RS Ophiuchi, up to 1 month after its 2021 outburst, observed using the High Energy Stereoscopic System (H.E.S.S.). The temporal profile of VHE emission is similar to that of lower-energy giga-electron volt emission, indicating a common origin, with a 2-day delay in peak flux. These observations constrain models of time-dependent particle energization, favoring a hadronic emission scenario over the leptonic alternative. Shocks in dense winds provide favorable environments for efficient acceleration of cosmic rays to very high energies.

6.
Science ; 372(6546): 1081-1085, 2021 06 04.
Article in English | MEDLINE | ID: mdl-34083487

ABSTRACT

Gamma-ray bursts (GRBs), which are bright flashes of gamma rays from extragalactic sources followed by fading afterglow emission, are associated with stellar core collapse events. We report the detection of very-high-energy (VHE) gamma rays from the afterglow of GRB 190829A, between 4 and 56 hours after the trigger, using the High Energy Stereoscopic System (H.E.S.S.). The low luminosity and redshift of GRB 190829A reduce both internal and external absorption, allowing determination of its intrinsic energy spectrum. Between energies of 0.18 and 3.3 tera-electron volts, this spectrum is described by a power law with photon index of 2.07 ± 0.09, similar to the x-ray spectrum. The x-ray and VHE gamma-ray light curves also show similar decay profiles. These similar characteristics in the x-ray and gamma-ray bands challenge GRB afterglow emission scenarios.

7.
Physiol Meas ; 27(9): 817-27, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16868348

ABSTRACT

UNLABELLED: Previously reported comparisons between cardiac output (CO) results in patients with cardiac conditions measured by thoracic impedance cardiography (TIC) versus thermodilution (TD) reveal upper and lower limits of agreement with two standard deviations (2SD) of approximately +/-2.2 l min(-1), a 44% disparity between the two technologies. We show here that if the electrodes are placed on one wrist and on a contralateral ankle instead of on the chest, a configuration designated as regional impedance cardiography (RIC), the 2SD limit of agreement between RIC and TD is +/-1.0 l min(-1), approximately 20% disparity between the two methods. To compare the performances of the TIC and RIC algorithms, the raw data of peripheral impedance changes yielded by RIC in 43 cardiac patients were used here for software processing and calculating the CO with the TIC algorithm. The 2SD between the TIC and TD was +/-1.7 l min(-1), and after annexing the correcting factors of the RIC formula to the TIC formula, the disparity between TIC and TD further declined to +/-1.25 l min(-1). CONCLUSIONS: (1) in cardiac conditions, the RIC technology is twice as accurate as TIC; (2) the advantage of RIC is the use of peripheral rather than thoracic impedance signals, supported by correcting factors.


Subject(s)
Algorithms , Cardiac Output , Cardiography, Impedance/methods , Diagnosis, Computer-Assisted/methods , Software , Humans , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity
8.
Circulation ; 101(12): 1358-61, 2000 Mar 28.
Article in English | MEDLINE | ID: mdl-10736276

ABSTRACT

BACKGROUND: The objective was to assess the safety and efficacy of L-NMMA in the treatment of cardiogenic shock. METHODS: We enrolled 11 consecutive patients with cardiogenic shock that persisted after >24 hours from admission, despite coronary catheterization and primary percutaneous transluminal coronary revascularization, when feasible, and treatment with mechanical ventilation, intraaortic balloon pump (IABP), and high doses of catecholamines. L-NMMA was administered as an IV bolus of 1 mg/kg and continuous drip of 1 mg. kg(-1). h(-1) for 5 hours. Treatment with catecholamines, mechanical ventilation, and IABP was kept constant throughout the study. RESULTS: Within 10 minutes of L-NMMA administration, mean arterial blood pressure (MAP) increased from 76+/-9 to 109+/-22 mm Hg (+43%). Urine output increased within 5 hours from 63+/-25 to 156+/-63 cc/h (+148%). Cardiac index decreased during the steep increase in MAP from 2. 0+/-0.5 to 1.7+/-0.4 L/(min. m(2)) (-15%); however, it gradually increased to 1.85+/-0.4 L/(min. m(2)) after 5 hours. The heart rate and the wedge pressure remained stable. Twenty-four hours after L-NMMA discontinuation, MAP (+36%) and urine output (+189%) remained increased; however, cardiac index returned to pretreatment level. No adverse events were detected. Ten out of eleven patients could be weaned off mechanical ventilation and IABP. Eight patients were discharged from the coronary intensive care unit, and seven (64%) were alive at 1-month follow-up. CONCLUSIONS: L-NMMA administration in patients with cardiogenic shock is safe and has favorable clinical and hemodynamic effects.


Subject(s)
Enzyme Inhibitors/therapeutic use , Shock, Cardiogenic/drug therapy , omega-N-Methylarginine/therapeutic use , Aged , Blood Pressure/drug effects , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/adverse effects , Female , Heart Rate/drug effects , Humans , Male , Pulmonary Wedge Pressure/drug effects , Treatment Outcome , Urine , omega-N-Methylarginine/administration & dosage , omega-N-Methylarginine/adverse effects
9.
J Am Coll Cardiol ; 36(3): 832-7, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10987607

ABSTRACT

OBJECTIVE: To determine the feasibility, safety and efficacy of bilevel positive airway ventilation (BiPAP) in the treatment of severe pulmonary edema compared to high dose nitrate therapy. BACKGROUND: Although noninvasive ventilation is increasingly used in the treatment of pulmonary edema, its efficacy has not been compared prospectively with newer treatment modalities. METHODS: We enrolled 40 consecutive patients with severe pulmonary edema (oxygen saturation <90% on room air prior to treatment). All patients received oxygen at a rate of 10 liter/min, intravenous (IV) furosemide 80 mg and IV morphine 3 mg. Thereafter patients were randomly allocated to receive 1) repeated boluses of IV isosorbide-dinitrate (ISDN) 4 mg every 4 min (n = 20), and 2) BiPAP ventilation and standard dose nitrate therapy (n = 20). Treatment was administered until oxygen saturation increased above 96% or systolic blood pressure decreased to below 110 mm Hg or by more than 30%. Patients whose conditions deteriorated despite therapy were intubated and mechanically ventilated. All treatment was delivered by mobile intensive care units prior to hospital arrival. RESULTS: Patients treated by BiPAP had significantly more adverse events. Two BiPAP treated patients died versus zero in the high dose ISDN group. Sixteen BiPAP treated patients (80%) required intubation and mechanical ventilation compared to four (20%) in the high dose ISDN group (p = 0.0004). Myocardial infarction (MI) occurred in 11 (55%) and 2 (10%) patients, respectively (p = 0.006). The combined primary end point (death, mechanical ventilation or MI) was observed in 17 (85%) versus 5 (25%) patients, respectively (p = 0.0003). After 1 h of treatment, oxygen saturation increased to 96 +/- 4% in the high dose ISDN group as compared to 89 +/- 7% in the BiPAP group (p = 0.017). Due to the significant deterioration observed in patients enrolled in the BiPAP arm, the study was prematurely terminated by the safety committee. CONCLUSIONS: High dose ISDN is safer and better than BiPAP ventilation combined with conventional therapy in patients with severe pulmonary edema.


Subject(s)
Isosorbide Dinitrate/administration & dosage , Positive-Pressure Respiration/methods , Pulmonary Edema/therapy , Vasodilator Agents/administration & dosage , Dose-Response Relationship, Drug , Female , Humans , Injections, Intravenous , Isosorbide Dinitrate/adverse effects , Isosorbide Dinitrate/therapeutic use , Male , Oxygen/blood , Positive-Pressure Respiration/adverse effects , Pulmonary Edema/blood , Pulmonary Edema/drug therapy , Treatment Outcome , Vasodilator Agents/adverse effects , Vasodilator Agents/therapeutic use
10.
Clin Pharmacol Ther ; 62(2): 187-93, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9284855

ABSTRACT

OBJECTIVE: To evaluate the safety and efficacy of low-dose dopamine, high-dose furosemide, and their combination in the treatment of refractory congestive heart failure. METHODS: Twenty consecutive patients with refractory congestive heart failure were randomized to receive intravenous low-dose (4 micrograms/kg/min) dopamine combined with low-dose (80 mg/day) oral furosemide (group A; n = 7), intravenous low-dose dopamine with medium-dose furosemide (5 mg/kg/day through continuous intravenous administration; group B; n = 7), or high-dose furosemide (10 mg/kg/day through continuous intravenous administration; group C; n = 6). RESULTS: The three groups showed similar improvement in signs and symptoms of congestive heart failure, urinary output (2506 +/- 671 ml/24 hr, mean +/- SD) and weight loss (3.3 +/- 2.3 kg) after 72 hours of therapy. Mean arterial blood pressure (MAP) decreased by 14% +/- 8% and 15% +/- 6% in groups B and C, respectively, but increased by 4% +/- 15% in group A (p = 0.017). Renal function deteriorated significantly in groups B and C: creatinine clearance decreased by 41% +/- 23% and 42% +/- 23%, respectively, but increased by 14% +/- 35% in group A (p = 0.0074). MAP decrease was positively correlated with the decrease in creatinine clearance (r = 0.7; p = 0.0007). Patients in group B and C had more hypokalemia than group A. Two patients in group C sustained acute oliguric renal failure and one patient in group B died suddenly while sustaining severe hypokalemia. CONCLUSION: Combined low-dose intravenous dopamine and oral furosemide have similar efficacy but induce less renal impairment and hypokalemia than higher doses of intravenous furosemide taken either alone or with low-dose dopamine. The renal impairment induced by intravenous furosemide is probably related to its hypotensive effect in patients with refractory congestive heart failure.


Subject(s)
Acute Kidney Injury/chemically induced , Diuretics/adverse effects , Dopamine/adverse effects , Furosemide/adverse effects , Heart Failure/drug therapy , Acute Kidney Injury/physiopathology , Administration, Oral , Aged , Blood Pressure/drug effects , Diuretics/administration & dosage , Diuretics/therapeutic use , Dopamine/administration & dosage , Dopamine/therapeutic use , Drug Therapy, Combination , Female , Furosemide/administration & dosage , Furosemide/therapeutic use , Humans , Infusions, Intravenous , Kidney/drug effects , Kidney/physiopathology , Male , Prospective Studies , Safety , Weight Loss/drug effects
11.
Int J Radiat Oncol Biol Phys ; 27(3): 531-5, 1993 Oct 20.
Article in English | MEDLINE | ID: mdl-8226145

ABSTRACT

PURPOSE: This study is a dosimetric review of our experience incorporating both external beam radiotherapy and endobronchial brachytherapy in the treatment of inoperable endobronchial obstructing lung cancer. METHODS AND MATERIALS: Sixty-five patients with symptomatic inoperable endobronchial obstructing lung cancer received combined external beam radiotherapy and temporary endobronchial iridium (Ir)-192 implants between February 1987 and May 1991. External beam irradiation doses ranged from 55 to 66 Gy. Patients were given 2 to 4 temporary Ir-192 endobronchial implants at the site of endobronchial obstruction. Individual implant doses ranged from 2.7 to 10 Gy. Total implant doses ranged from 6 to 35 Gy. Total treatment doses ranged from 61 to 96.6 Gy. RESULTS: Sixty-three percent of patients had a complete local endobronchial response to treatment and 23% had a partial response. Forty-seven percent of patients receiving a total dose of less than 70 Gy experienced a complete local endobronchial response to treatment while 83% of patients receiving a total dose of 85 Gy or greater experienced a complete local endobronchial response to treatment. Sixty-six percent experienced an improvement in their performance status using an Eastern Cooperative Oncology Group performance scale. Survival from the end of treatment was 38% at 1 year and 23% at 2 years, with the median survival at 8 months. Complications occurred in 9/65 (14%) of patients; 0% in patients receiving a total dose of less than 70 Gy, 10% in patients receiving a total dose of 70 to 84.99 Gy, and 24% of patients receiving a total dose of 85 Gy or higher. CONCLUSION: The data from this study again confirms the feasibility of this form of treatment for inoperable endobronchial obstructing lung cancer. In addition, there appears to be a dose response for both local response and complications.


Subject(s)
Brachytherapy , Lung Neoplasms/radiotherapy , Radiotherapy Dosage , Brachytherapy/adverse effects , Dose-Response Relationship, Radiation , Humans , Lung Neoplasms/mortality , Radiotherapy/adverse effects , Survival Rate
12.
Int J Radiat Oncol Biol Phys ; 9(10): 1477-80, 1983 Oct.
Article in English | MEDLINE | ID: mdl-6195138

ABSTRACT

Between 1966 and 1981, 20 patients (191 lesions) underwent palliative radiation therapy for control of biopsy-proven cutaneous mycosis fungoides. Six patients (47 lesions) and an additional 34 lesions from the remaining 14 patients with complete response to treatment were excluded from the study because of follow-up of less than one year. Included in the remaining 110 lesions were all recurrences and all partial responses. The modalities for treatment included superficial X rays, Cobalt-60 or electron beam irradiation. The total tumor doses employed ranged from 600-4000 cGy. The 110 lesions (14 patients) were retrospectively analyzed to determine the dose required for local control of the lesions. Fifty-three percent of the lesions were classified as plaques, 20% as tumors less than or equal to 3 cm in diameter, and 27% as tumors greater than 3 cm in diameter. Complete response to treatment was observed in 95% of the plaque lesions, 95% of the tumors less than or equal to 3 cm in diameter and 93% of tumor greater than 3 cm in diameter. A complete response to treatment was noted in all lesions receiving greater than 2000 cGy. In the total population of lesions having a complete response, a local infield recurrence rate of 42% was noted in the group receiving less than or equal to 1000 cGy, 32% in those receiving 1001-2000 cGy, 21% in those receiving 2001-3000 cGy, and 0% in the group receiving greater than 3000 cGy. No infield recurrence was seen when the treated lesion received a total tumor dose greater than or equal to TDF of 49. Of those lesions which recurred, the mean time to recurrence for the first three dose ranges above were 5 months, 10 months and 16 months respectively. Eighty-three percent of the 30 recurrences were seen within one year of treatment; 100% of the recurrences occurred within two years of treatment. The data from this study indicate that tumor doses equivalent to at least 3000 cGy at 200 cGy per fraction, five fractions per week (TDF greater than or equal to 49) are needed for adequate local control of cutaneous mycosis fungoides lesions.


Subject(s)
Mycosis Fungoides/radiotherapy , Palliative Care/methods , Skin Neoplasms/radiotherapy , Cobalt Radioisotopes/therapeutic use , Dose-Response Relationship, Radiation , Electrons , Humans , Radiotherapy Dosage , Retrospective Studies , Time Factors
13.
Int J Radiat Oncol Biol Phys ; 11(12): 2177-81, 1985 Dec.
Article in English | MEDLINE | ID: mdl-4066451

ABSTRACT

Application of a contact X ray therapy unit for endocavitary irradiation of selected rectal carcinomas is gaining acceptance as a treatment of choice. The patient is placed on a proctoscopic table in the surgical suite and the anus is anesthetized and dilated to allow insertion of a 3 cm diameter proctoscope designed to admit the X ray tube. The measured half-value layer for 50 kVp X rays filtered by 1.0 mm of aluminum was determined to be 0.65 mm of aluminium. The dose rate at the end of the 4.0 cm source-skin-distance (SSD) cone was measured to be on the order of 1000 rad/minute. Radiation surveys performed for several treatment geometries indicate that exposure rate levels in the environs immediately around the patient can be quite high. Radiation measurements were made for the following locations: where the radiotherapist stands holding the X ray tube; at the side of the patient where the technologist or any supporting personnel might stand; and at the patient's posterior surface in the direction where the anesthesiologist might stand. Radiation levels ranged from 0.001 to 1.0 roentgen (R) per hour and depend primarily on the depth and angle of the X ray tube inserted into the rectum.


Subject(s)
Brachytherapy/instrumentation , Rectal Neoplasms/radiotherapy , Brachytherapy/adverse effects , Humans , Mathematics , Proctoscopy , Radiation Protection , Radiotherapy Dosage , Scattering, Radiation
14.
Am J Cardiol ; 85(8): 953-6, 2000 Apr 15.
Article in English | MEDLINE | ID: mdl-10760333

ABSTRACT

The purpose of the study was to assess the results of percutaneous transluminal coronary angioplasty (PTCA), performed with a single intravenous bolus of 2,500 U of heparin, in a nonemergency PTCA cohort. Three hundred of 341 consecutive patients (87.9%) undergoing PTCA were prospectively enrolled in the study. They received heparin, 2,500-U intravenous bolus, before PTCA, with intention of no additional heparin administration. Patient and lesion characteristics as well as PTCA results were evaluated independently by 2 physicians. Patients were followed up by structured telephone questionnaires at 1 and 6 months after PTCA. Mean activated clotting time obtained 5 minutes after heparin administration was 185+/-19 seconds (range 157 to 238). There were 3 (1%) in-hospital major adverse cardiovascular events: 2 deaths (0.66%), 1 (0.33%) Q-wave myocardial infarction. Emergency coronary surgery and stroke were not reported. Six patients (2%) experienced abrupt coronary occlusion within 14 days after PTCA, warranting repeat target vessel revascularization. Angiographic and clinical success were achieved in 96% and 93.3%, respectively. No bleeding or vascular complications were recorded. Six-month follow-up (184 patients) revealed 3 cardiac deaths (1 arrhythmic, 2 after cardiac surgery), 1 Q-wave myocardial infarction, and 9.7% repeat target vessel revascularization. This study suggests that very low doses of heparin and reduced activated clotting time target values are safe in non-emergency PTCA, and can reduce bleeding complications, hospital stay, and costs. Larger, randomized, double-blind heparin dose optimization studies need to confirm this notion.


Subject(s)
Angioplasty, Balloon, Coronary , Anticoagulants/administration & dosage , Coronary Disease/therapy , Heparin/administration & dosage , Anticoagulants/therapeutic use , Cohort Studies , Coronary Angiography , Coronary Disease/blood , Coronary Disease/diagnostic imaging , Female , Follow-Up Studies , Heparin/therapeutic use , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Safety , Time Factors , Whole Blood Coagulation Time
15.
Am J Cardiol ; 82(9): 1024-9, 1998 Nov 01.
Article in English | MEDLINE | ID: mdl-9817475

ABSTRACT

Sixty consecutive normotensive patients with unstable angina pectoris, who were on continuous intravenous isosorbide dinitrate (ISDN) treatment and had not previously received angiotensin II receptor antagonists, angiotensin-converting enzyme (ACE) inhibitors, or diuretics were randomly assigned to treatment groups receiving intravenous ISDN for 72 hours. No additional treatment was given to group A (n = 15). Captopril, in a test dose of 6.25 mg, and followed by 12.5 mg 3 times daily for 24 hours and 25 mg 3 times daily for the next 24 hours, was given to group B (n = 15). The same dose of captopril plus 40 mg of furosemide in the morning were given to group C (n = 15). Losartan, in a single dose of 25 mg/day and increased to 50 mg after 24 hours was given to group D (n = 15). Nitrate tolerance was evaluated at 24-hour intervals at trough levels of each of the drugs by administering intravenous ISDN (1 mg bolus dose every 4 minutes) and recording the total ISDN test dose required to decrease the mean arterial blood pressure by > or =10%. Treatment with continuous ISDN only (group A) induced nitrate tolerance. The ISDN (mean +/- SD) test dose was 3.5 +/- 1.8 mg at baseline, increasing to 4.9 +/- 2.4 mg at 24 hours, and 8.0 +/- 3.0 mg at 48 hours. The addition of increasing doses of captopril to the continuous ISDN treatment (group B) completely prevented nitrate tolerance. Losartan, however, did not attenuate nitrate tolerance at 24 hours and attenuated it only partially at 48 hours. The addition of furosemide to captopril had no further effect on nitrate tolerance. Of 15 patients in group A (ISDN only), 4 (27%) experienced recurrent ischemic events requiring urgent coronary catheterization. No such events were recorded in group B (captopril), but did occur in 1 patient in each of group C (captopril plus furosemide) and D (losartan) (p = 0.083). Thus, the addition of captopril to the ISDN treatment regimen prevented tolerance to nitrates and improved angina control with apparent safety. Losartan also decreased nitrate tolerance, although to a lesser extent, and also improved angina control. The addition of furosemide to captopril conferred no further benefit.


Subject(s)
Angina, Unstable/prevention & control , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Captopril/therapeutic use , Diuretics/therapeutic use , Furosemide/therapeutic use , Isosorbide Dinitrate/pharmacology , Losartan/therapeutic use , Adult , Aged , Drug Therapy, Combination , Drug Tolerance , Female , Humans , Male , Middle Aged , Prospective Studies
16.
Eur J Heart Fail ; 3(4): 457-61, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11511432

ABSTRACT

OBJECTIVE: This study investigated the effect of tezosentan (an intravenous endothelin-1 receptor antagonist) on vascular resistance and cardiac function and determined the dose response in patients with stable congestive heart failure (CHF) due to left ventricular systolic dysfunction. METHODS: In a double-blind fashion, tezosentan or placebo were administered in ascending doses (5, 20, 50, 100 mg h(-1)) to 38 CHF (NYHA class III) patients with ejection fraction or=15 mmHg. Systemic vascular resistance index (SVRi) was estimated as mean arterial blood pressure [(MAP-right atrial pressure)/cardiac index (CI)]. Cardiac function was assessed as cardiac power index (Cpi), calculated as pressure x flow (MAP x CI), where MAP represents pressure and CI represents cardiovascular flow. RESULTS AND DISCUSSION: Compared to the placebo, tezosentan induced a dose-dependent decrease in SVRi (-32%), an increase in Cpi (+20%) and a small decrease in MAP (-9%). By contrast, patients treated with nitrate vasodilators or nesiritide (a natriuretic peptide) showed a decrease in SVRi not accompanied by a significant increase in Cpi leading to a steep decrease in MAP. CONCLUSIONS: The use of Cpi in the assessment of the hemodynamic effects of tezosentan, provides a useful alternative characterization of the complex influences of vasodilators on cardiac function in patients with CHF.


Subject(s)
Endothelin Receptor Antagonists , Heart Failure/drug therapy , Hypotension/prevention & control , Pyridines/administration & dosage , Tetrazoles/administration & dosage , Adult , Aged , Blood Pressure/drug effects , Confidence Intervals , Dose-Response Relationship, Drug , Double-Blind Method , Female , Follow-Up Studies , Heart Failure/complications , Heart Failure/diagnosis , Heart Function Tests , Humans , Infusions, Intravenous , Male , Middle Aged , Probability , Receptors, Endothelin/administration & dosage , Reference Values , Severity of Illness Index , Stroke Volume/drug effects , Treatment Outcome , Vascular Resistance/drug effects
17.
FEMS Immunol Med Microbiol ; 27(2): 163-9, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10640612

ABSTRACT

Conventional in vivo assays to determine the relative pathogenicity of yeast isolates rely upon the use of a range of mammalian species. The purpose of the work presented here was to investigate the possibility of using an insect (Galleria mellonella) as a model system for in vivo pathogenicity testing. The haemolymph of G. mellonella larvae was inoculated with PBS containing different concentrations of stationary phase yeasts of the genus Candida by injection at the last pro-leg. Larvae were incubated at 30 degrees C and monitored over 72 hours. Results indicate that G. mellonella can be killed by the pathogenic yeast Candida albicans and by a range of other Candida species but not to a significant extent by the yeast Saccharomyces cerevisiae. The kill kinetics for larvae inoculated with clinical and laboratory isolates of C. albicans indicate the former class of isolates to be more pathogenic. Differences in the relative pathogenicity of a range of Candida species may be distinguished using G. mellonella as a model. This work indicates that G. mellonella may be employed to give results consistent with data previously obtained using mammals in conventional in vivo pathogenicity testing. Larvae of G. mellonella are inexpensive to culture, easy to manipulate and their use may reduce the need to employ mammals for routine in vivo pathogenicity testing with a concomitant reduction in mammalian suffering.


Subject(s)
Candida/pathogenicity , Moths/microbiology , Saccharomyces cerevisiae/pathogenicity , Animals , Candida albicans/isolation & purification , Candida albicans/pathogenicity , Models, Biological , Moths/physiology , Virulence
18.
Gen Hosp Psychiatry ; 23(4): 215-22, 2001.
Article in English | MEDLINE | ID: mdl-11543848

ABSTRACT

We examined a novel hypothesis that links symptoms of MI-related posttraumatic stress disorder (PTSD) to nonadherence. According to this hypothesis, patients who are traumatized by their medical illness do not take their medications as prescribed. As a part of the avoidance dimension of PTSD, patients who are traumatized may avoid being reminded of the MI by not taking the medication. MI survivors were prospectively followed for 6 months to 1 year. Adherence was assessed by pill count of Captopril. Demographic variables, medical risk factors, PTSD, and other psychiatric symptom dimensions were evaluated during follow-up. One hundred two of 140 recruited patients completed follow-up. Nonadherence to Captopril was associated with poor medical outcome (r=.93, P=.006). Above-Threshold PTSD symptoms were associated with nonadherence to medications (P=.05). No other psychiatric symptom dimensions were independently associated with nonadherence. Nonadherence to medications predicts adverse outcome during the first year after an acute MI. Nonadherence is associated with PTSD symptoms, which may either be a marker for or a cause of nonadherence. Treatment of PTSD may prove to be a useful approach for improving adherence.


Subject(s)
Myocardial Infarction/psychology , Myocardial Infarction/therapy , Patient Compliance/statistics & numerical data , Stress Disorders, Post-Traumatic/diagnosis , Survivors/statistics & numerical data , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myocardial Infarction/mortality , Prospective Studies , Stress Disorders, Post-Traumatic/psychology , Survival Rate
19.
Eur J Cardiothorac Surg ; 12(1): 31-9, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9262078

ABSTRACT

OBJECTIVE: Cardiopulmonary bypass in coronary artery bypass graft operations may adversely affect the outcome especially in high-risk patients. The purpose of this study is to evaluate results of coronary artery bypass performed without cardiopulmonary bypass, in a relatively high-risk cohort, and to identify predictors of unfavorable outcome. METHOD: Three hundred and thirteen (313) patients, 246 (79%) of whom had high-risk conditions, who have a coronary anatomy suitable for coronary artery bypass surgery without cardiopulmonary bypass, underwent this procedure between December 1991 and July 1995. Mean number of grafts/patient was 1.8 (1-5), and only 71 patients (23%) received a graft to the circumflex coronary system. RESULTS: Early unfavorable outcome events included operative mortality (12 patients, 3.8%), nonfatal perioperative myocardial infarction (eight patients, 2.6%), emergency reoperation (three patients, 0.9%), sternal infection (five patients, 1.6%), and nonfatal stroke (two patients, 0.6%). Multivariate analysis revealed angina pectoris class IV (odds ratio 5.4) and age > or = 70 years (odds ratio 5.0) as independent predictors of early mortality. Preoperative risk factors such as repeat coronary artery bypass grafting (50 patients, 16%), ejection fraction < or = 0.35 (85 patients, 27%), acute myocardial infarction (86 patients, 28%), cardiogenic shock (ten patients, 3.2%), chronic renal failure (25 patients, 8%), chronic obstructive pulmonary disease (20 patients, 6%), and peripheral vascular disease (51 patients, 16%) did not increase early mortality. During 33 months of follow-up (range 1-57 months), there were 42 deaths, at least 16 cardiac-related (one and four years actuarial survival of 90% and 76% respectively), and 39 patients (12.5%) in whom angina returned. Calcified aorta (odds ratio 2.6) and old myocardial infarction (odds ratio 1.8) were independent predictors of overall unfavorable events. CONCLUSIONS: Coronary artery bypass grafting without cardiopulmonary bypass can be performed with relatively low operative mortality in certain high-risk subgroups of patients; however, an increased risk of graft occlusion is a potential disadvantage. This procedure should therefore be considered only for patients with suitable coronary anatomy, in whom cardiopulmonary bypass poses a high risk. Although the risk of stroke is relatively low, the procedure is still hazardous for patients aged 70 years and over.


Subject(s)
Cardiopulmonary Bypass , Coronary Artery Bypass/methods , Adult , Age Factors , Aged , Aged, 80 and over , Coronary Artery Bypass/mortality , Female , Humans , Male , Middle Aged , Multivariate Analysis , Patient Selection , Postoperative Complications/mortality , Risk Factors , Shock, Cardiogenic/mortality , Survival Analysis , Time Factors , Treatment Outcome
20.
Br J Biomed Sci ; 57(3): 241-9, 2000.
Article in English | MEDLINE | ID: mdl-11050778

ABSTRACT

The yeast Candida albicans is an opportunistic fungal pathogen that is capable of inducing a range of superficial and systemic diseases in the immunocompromised host. Although it displays a variety of virulence factors, one--the ability to adhere to host tissue--is considered essential in the early stages of colonisation and tissue invasion. Adherence is achieved by a combination of specific (ligand-receptor interactions) and non-specific (electrostatic charge, van der Waals forces) mechanisms which allow the yeast to attach to a wide range of tissue types and inanimate surfaces. Conventional methods for treating disease cause by C. albicans rely upon the use of antifungal drugs designed to kill the yeast or arrest its growth. An alternative approach, aimed at disrupting the adherence of the yeast to host tissue in cases of superficial infection, may have potential for controlling disease, particularly in situations where the unattached fungal cell can be removed from the affected site, either by the flushing action of the oropharynx or by the production of mucus in the vagina.


Subject(s)
Candida albicans/pathogenicity , Antifungal Agents/pharmacology , Candidiasis/drug therapy , Cell Adhesion/drug effects , Cell Adhesion/physiology , Humans , Virulence
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