CineCT platform for in vivo and ex vivo measurement of 3D high resolution Lagrangian strains in the left ventricle following myocardial infarction and intramyocardial delivery of theranostic hydrogel.

Myocardial infarction (MI) produces acute changes in strain and stiffness within the infarct that can affect remote areas of the left ventricle (LV) and drive pathological remodeling. We hypothesized that intramyocardial delivery of a hydrogel within the MI region would lower wall stress and reduce adverse remodeling in Yorkshire pigs (n = 5). 99mTc-Tetrofosmin SPECT imaging defined the location and geometry of induced MI and border regions in pigs, and in vivo and ex vivo contrast cine computed tomography (cineCT) quantified deformations of the LV myocardium. Serial in vivo cineCT imaging provided data in hearts from control pigs (n = 3) and data from pigs (n = 5) under baseline conditions before MI induction, post-MI day 3, post-MI day 7, and one hour after intramyocardial delivery of a hyaluronic acid (HA)-based hydrogel with shear-thinning and self-healing properties to the central infarct area. Isolated, excised hearts underwent similar cineCT imaging using an ex vivo perfused heart preparation with cyclic LV pressurization. Deformations were evaluated using nonlinear image registration of cineCT volumes between end-diastole (ED) and end-systole (ES), and 3D Lagrangian strains were calculated from the displacement gradients. Post-MI day 3, radial, circumferential, maximum principal, and shear strains were reduced within the MI region (p < 0.04) but were unchanged in normal regions (p > 0.6), and LV end diastolic volume (LV EDV) increased (p = 0.004), while ejection fraction (EF) and stroke volume (SV) decreased (p < 0.02). Post-MI day 7, radial strains in MI border zones increased (p = 0.04) and dilation of LV EDV continued (p = 0.052). There was a significant negative linear correlation between regional radial and maximum principal/shear strains and percent infarcted tissue in all hearts (R2 > 0.47, p < 0.004), indicating that cineCT strain measures could predict MI location and degree of injury. Post-hydrogel day 7 post-MI, LV EDV was significantly reduced (p = 0.009), EF increased (p = 0.048), and radial (p = 0.021), maximum principal (p = 0.051), and shear strain (p = 0.047) increased within regions bordering the infarct. A smaller strain improvement within the infarct and normal regions was also noted on average along with an improvement in SV in 4 out of 5 hearts. CineCT provides a reliable method to assess regional changes in strains post-MI and the therapeutic effects of intramyocardial hydrogel delivery.

Decreased elastic energy storage, not increased material stiffness, characterizes central artery dysfunction in fibulin-5 deficiency independent of sex.

Central artery stiffness has emerged over the past 15 years as a clinically significant indicator of cardiovascular function and initiator of disease. Loss of elastic fiber integrity is one of the primary contributors to increased arterial stiffening in aging, hypertension, and related conditions. Elastic fibers consist of an elastin core and multiple glycoproteins; hence defects in any of these constituents can adversely affect arterial wall mechanics. In this paper, we focus on mechanical consequences of the loss of fibulin-5, an elastin-associated glycoprotein involved in elastogenesis. Specifically, we compared the biaxial mechanical properties of five central arteries-the ascending thoracic aorta, descending thoracic aorta, suprarenal abdominal aorta, infrarenal abdominal aorta, and common carotid artery-from male and female wild-type and fibulin-5 deficient mice. Results revealed that, independent of sex, all five regions in the fibulin-5 deficient mice manifested a marked increase in structural stiffness but also a marked decrease in elastic energy storage and typically an increase in energy dissipation, with all differences being most dramatic in the ascending and abdominal aortas. Given that the primary function of large arteries is to store elastic energy during systole and to use this energy during diastole to work on the blood, fibulin-5 deficiency results in a widespread diminishment of central artery function that can have significant effects on hemodynamics and cardiac function.

Aortic pseudo-aneurysm with Aspergillus aortitis. An unusual complication of coronary bypass surgery.

This is the first report of fatal postoperative Aspergillus infection in an aortic pseudoaneurysm associated with a jet lesion produced by a deformed, but hemodynamically normal aortic valve. Widespread arterial embolization was the principal feature and resulted in death on the 12th hospital day due to massive thromboembolism to the brain three months after successful coronary bypass surgery. Possible sources of such infections and the potential effect of the jet lesion are discussed.

Septic endarteritis due to intra-arterial catheters for cancer chemotherapy. I. Evaluation of an outbreak. II. Risk factors, clinical features and management, III. Guidelines for prevention.

A cluster of three cases of staphylococcal septic endarteritis originating from percutaneously inserted brachial artery catheters for regional cancer chemotherapy prompted an epidemiologic and clinical study of bacteremic infections associated with this therapeutic modality. Nine cases were identified over a 3 1/2-year period (1.6% of all catheterizations), all caused by Staphylococcus aureus. The cluster followed discontinuation of hexachlorophene for scrub of the extremity prior to cannulation; phage-typing suggested the three cases were caused by the patients' own strains of Staphylococcus. These infections produced a distinctive clinical syndrome which facilitates implicating the catheter in the genesis of fever occurring in a patient receiving intra-arterial chemotherapy: early localized pain (89%) and hemorrhage (78%), and Osler's nodes distally (44%), later followed by local inflammation (78%), purulence (56%) and signs of systemic sepsis (100%) (each factor, p less than or equal to .005). Duration of cannulation did not influence susceptibility to infection. However, difficult cannulations or need for repositioning the catheter (p = .0096), prior radiation therapy (p = .033), leukopenia (p less than .05) and hypoalbuminemia (p less than .05) were all associated with septicemia. In the 25 months since implementation of specific control measures, there have been no further catheter-related septicemia in 310 catheterization (p less than .001). Guide-lines for prevention and management of these infections are provided.

Hospital use of antimicrobial drugs. Survey at 19 hospitals and results of antimicrobial control program.

Costs and use of antimicrobial agents in 1976 at 19 hospitals were surveyed by review of pharmacy records. Total costs of antimicrobial drugs at individual hospitals ranged from $0.65 to $1.75 per patient day and accounted for 16% to 41% of total pharmacy drug costs. There was marked variation among hospitals in use of specific antimicrobial agents, especially cephalosporins and clindamycin. The cephalosporin and aminoglycoside antibiotics accounted for 66% of the total cost of antimicrobial agents. An 18-month antimicrobial drug control program at one hospital decreased antimicrobial drug costs by 31%. The major effect was in reducing cephalosporin use. The results of the control program document that a significant portion of hospital antimicrobial use is inappropriate and can be eliminated without apparent detriment to patient care.

Pseudomonas aeruginosa bacteremia in a dialysis unit. 1. Recognition of cases, epidemiologic studies and attempts at control.

Infections commonly occur in patients undergoing dialysis and have been related to diminished host resistance of uremic patients, the arteriovenous fistulas and bacteriologic contamination of dialysis fluids. The occurrence of four cases of bacteremia due to Pseudomonas, three of which were type 7, and the presence of this serotype in the dialysis fluids suggested an important association between infection and growth of bacteria in the fluids. Attempts to reduce levels of bacteria in the dialysis fluid were unsuccessful using dialysate free of glucose in clinical trial, despite in vitro studies demonstrating poor growth of Pseudomonas in this medium. A filter placed with the recirculating system was only partially successful. The second paper of this series traces the portal of entry of bacteria from dialysate to the blood through reutilized coils.

Pseudomonas aeruginosa bacteremia in a dialysis unit. 11. Relationship to reuse of coils.

Blood for culture was obtained over a six week period from 17 patients undergoing long-term hemodialysis. Bacteremia was detected during 18 of 201 dialyses. Blood drawn during fifteen of these dialyses contained pseudomonas aeruginosa. Ten of the 17 patients (59 per cent) had a Pseudomonas bacteremia some time during the study. Only one patient was symptomatic. The frequency of positive cultures was related to reuse of coils. No cultures were positive until after the fifth use, but by the tenth use, 41 per cent of the dialyses were associated with bacteremia. All coils that were used repeatedly and 32 of 48 of those used only once, grew Ps. aeruginosa when filled with media and incubated. This suggests that the coils were inoculated during dialysis and that benzalkonium chloride, the sterilizing agent, was unable to eradicate this organism. With repeated uses, the number of residual bacteria in the coil became large enough to cause detectable bacteremia during dialysis.

Pharmacokinetics of minocycline in renal failure.

The pharmacokinetics of minocycline have been studied after single intravenous infusions and repeated oral doses to human subjects with varying degrees of renal impairment. There was no evidence of reduced drug clearance with reduced renal function after intravenous doses although there appeared to be an increase in the tissue distribution of antibiotic in the body in uremia. After identical multiple oral dosage regimens serum levels of antibiotic were comparable in normal and mildly uremic subjects. There was no evidence of renal toxicity in normal or uremic subjects with the repeated dosage regimen used.

Needle aspiration in the diagnosis of soft tissue infections.

Diagnosis of soft tissue infections is often delayed or made incorrectly because of reliance on indirect means to determine the etiologic agent. A rapid, speific method is the needle aspiration of these lesions combined with Gram-stain and culture studies. More frequent use of this direct method should facilitate diagnosis and improve treatment. Seven case studies are present to illustrate the usefulness of this technique.