Persistent bi-coronary Thebesian veins to the left ventricle.

In this image case we describe a relatively rare vascular malformation known of as Thebesian veins, which in some cases could cause cardiac ischemia and ventricular arrhytmias.

Early mitral valve repair versus watchful waiting in patients with severe asymptomatic organic mitral regurgitation; rationale and design of the Dutch AMR trial, a multicenter, randomised trial.

BACKGROUND: Asymptomatic severe mitral valve (MV) regurgitation with preserved left ventricular function is a challenging clinical entity as data on the recommended treatment strategy for these patients are scarce and conflicting. For asymptomatic patients, no randomised trial has been performed for objectivising the best treatment strategy. METHODS: The Dutch AMR (Asymptomatic Mitral Regurgitation) trial is a multicenter, prospective, randomised trial comparing early MV repair versus watchful waiting in asymptomatic patients with severe organic MV regurgitation. A total of 250 asymptomatic patients (18-70 years) with preserved left ventricular function will be included. Intervention will be either watchful waiting or MV surgery. Follow-up will be 5 years. Primary outcome measures are all-cause mortality and a composite endpoint of cardiovascular mortality, congestive heart failure, and hospitalisation for non-fatal cardiovascular and cerebrovascular events. Secondary outcome measures are total costs, cost-effectiveness, quality of life, echocardiographic and cardiac magnetic resonance parameters, exercise tests, asymptomatic atrial fibrillation and brain natriuretic peptide levels. Additionally, the complication rate in the surgery group and rate of surgery in the watchful waiting group will be determined. IMPLICATIONS: The Dutch AMR trial will be the first multicenter randomised trial on this topic. We anticipate that the results of this study are highly needed to elucidate the best treatment strategy and that this may prove to be an international landmark study.

Principles of selection and use of antibacterial agents. In vitro activity and pharmacology.

The selection of an antimicrobial treatment regimen is based on many factors, including the nature of the infection, the identity and susceptibility pattern of the infecting organisms, and the pharmacokinetics and pharmacodynamics of the antibacterial drugs. This article discusses principles of susceptibility testing, pharmacology, and monitoring of therapy.

Principles of selection and use of antibacterial agents.

Treatment of infection involves a complex interaction among the infecting organism (susceptibility to the therapeutic agent), host factors (immune function, site of infection, renal and hepatic metabolism), and pharmacokinetics (rate of absorption, distribution and excretion). Successful therapy requires careful consideration of these factors, and unsuccessful treatment should invoke a careful reanalysis of them.

Comparing subcutaneous danaparoid with intravenous unfractionated heparin for the treatment of venous thromboembolism. A randomized controlled trial.

OBJECTIVE: To compare the efficacy and safety of two subcutaneous doses of danaparoid with that of continuous intravenous administration of unfractionated heparin in the treatment of venous thromboembolism. DESIGN: An open-label, randomized, multicenter clinical trial. SETTING: One university hospital and two university-affiliated hospitals. PATIENTS: 209 patients suspected to have venous thromboembolism. Of these, 188 had a confirmed diagnosis (by ventilation-perfusion lung scan and ultrasonography or contrast venography of the leg) and received study medication. INTERVENTIONS: Patients were randomly assigned to either low-dose danaparoid (intravenous loading dose of 1250 U followed by 1250 U administered subcutaneously twice daily [n = 65]); high-dose danaparoid (intravenous loading dose of 2000 U followed by 2000 U administered subcutaneously twice daily [n = 63]); or unfractionated heparin (intravenous loading dose of 2500 U followed by dose-adjusted continuous infusion [n = 60]). Treatment lasted at least 5 days and was continued until anticoagulation (achieved with acenocoumarol) was adequate. MEASUREMENTS: Efficacy determined clinically and by repeated imaging tests on treatment days 5 to 8; safety determined by daily assessment for bleeding. RESULTS: Two lung scans were done in each of 179 patients; ultrasonography or venography of the leg was done twice in each of 173 patients; and both repeated leg and lung tests were done in 166 patients. A significant reduction in recurrence or extension of venous thromboembolism was seen in patients receiving high-dose danaparoid (8 of 63 [13%]) compared with patients receiving intravenous unfractionated heparin (17 of 60 [28%]; relative risk, 0.45 [95% CI, 0.21 to 0.96]). Four of 61 patients receiving high-dose danaparoid (7%) and 14 of 58 patients receiving unfractionated heparin (24%) had recurrence of pulmonary embolism (relative risk, 0.27 [CI, 0.09 to 0.78]); 3 of 58 patients receiving high-dose danaparoid (5%) and 6 of 54 patients receiving unfractionated heparin (11%) had recurrence of deep venous thrombosis (relative risk, 0.47 [CI, 0.12 to 1.77]). Occurrence of major and minor bleeding was similar in the three groups; major bleeding occurred in 1 patient receiving low-dose danaparoid, 1 patient receiving high-dose danaparoid, and 2 patients receiving heparin. CONCLUSIONS: Our results suggest that high-dose danaparoid is safer and more effective than unfractionated heparin for the treatment of venous thromboembolism.

Heterogeneous effects of exogenous lymphokines on lymphoproliferation of elderly subjects.

Although the ability of peripheral blood mononuclear cells of a population of elderly subjects (mean age 85.3) to proliferate in response to the T cell mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) is significantly reduced compared to young subjects (mean age 24.7), the response of the elderly subjects is heterogeneous. While 47% of the elderly subjects responded at about half the level of young controls, 15% responded at less than 20% the level and the remaining 38% responded comparably to young controls. Similar heterogeneity was observed in lymphokine production. However, there was no significant correlation between the level of proliferative response and production of either interleukin 2 (IL-2) or interferon gamma (IFN-g). In an effort to further explore the role of lymphokines in the decreased proliferative response of elderly subjects, various concentrations of exogenous IL-2 and/or IFN-gamma were added at the initiation of the mitogen stimulated cultures. Similar increases in both the level of response and the number of subjects demonstrating an increase was observed for both young and elderly subjects upon addition of either IL-2 or IFN-gamma. However, addition of a combination of IL-2 and IFN produced more pronounced effects in the elderly subjects. Approximately 1/3 of the elderly subjects who demonstrated decreased PHA-induced proliferation doubled their PHA induced proliferative response upon addition of a combination of lymphokines. The amounts of IL-2 and IFN-gamma required for this increase varied for each individual.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral temafloxacin versus vancomycin for therapy of experimental endocarditis caused by methicillin-resistant Staphylococcus aureus.

We compared oral temafloxacin, a new fluoroquinolone agent, with vancomycin, each with and without rifampin, in the therapy of rats with aortic valve endocarditis caused by a clinical isolate of methicillin-resistant Staphylococcus aureus. The temafloxacin, vancomycin, and rifampin MICs and MBCs were 0.78 and 1.56, 1.56 and 3.13, and less than 0.024 and 0.78 microgram/ml, respectively. The animals were classified into the following six treatment groups: vancomycin (60 mg/kg) +/- rifampin (6 mg/kg) each intramuscularly every 12 h for 5 days; temafloxacin (100 mg/kg) orally +/- rifampin (6 mg/kg) intramuscularly every 12 h for 5 days; rifampin (6 mg/kg) intramuscularly every 12 h for 5 days; and untreated controls. All regimens with either vancomycin or temafloxacin resulted in improved survival over controls, but only temafloxacin regimens resulted in a significant reduction in bacterial counts in vegetations. These data support further investigation of the efficacy of temafloxacin in treating serious infections caused by methicillin-resistant S. aureus.

Principles of selection and use of antibacterial agents.

The selection of an antimicrobial treatment regimen is based on many factors, including the nature of the infection, the identity and susceptibility pattern of the infecting organism, and the pharmacokinetics and pharmacodynamics of the drug(s). Principles of susceptibility testing, pharmacology, and monitoring of therapy are discussed in this article.

Effect of timing of transient diastolic changes in ventricular filling on LV performance in dogs.

The influence of acute volume changes during diastole on the contractile state of the left ventricle has been studied in the closed-chest dog. Volume changes were introduced by means of a servo-controlled pump system connected to the left ventricular cavity by an apical cannula. Pressure measurements were made in the left ventricle and aorta. Flow sensors in the mitral valve and around the ascending aorta monitored ventricular inflow and outflow patterns. The ventricular performance was evaluated in terms of the ratio between end-systolic pressure and end-systolic volume (P/Ves). By changing the time of occurrence of the volume interventions from the rapid filling phase of diastole to the atrial contraction phase, the relative contributions of rapid filling and atrial contraction to the mitral flow were changed. When the rapid filling was changed by the volume intervention, the effect on the contractile status of the heart, expressed as the P/Ves value, was small. In contrast, when the volume intervention took place during the atrial contraction phase, the effect on the P/Ves value was much larger. Comparison with muscle fiber experiments suggests that length-dependent calcium sensitivity of troponin and length-dependent conductivity of the sarcolemma are the underlying fundamental mechanisms. Therefore, we conclude that the influence of an intervention in ventricular filling on the inotropic state of the left ventricle is dependent on the timing of the intervention.

Postantibiotic effect of penicillin plus gentamicin versus Enterococcus faecalis in vitro and in vivo.

A persistent suppression of bacterial growth following a brief exposure to an antibiotic (postantibiotic effect [( PAE]) has been described for a variety of antibiotics and microorganisms. If a PAE is present in vivo, antibiotic levels in tissue at the site of infection may decrease below the MIC without bacterial regrowth in the latter portion of the dosing interval. In the present studies, a PAE was sought in vitro and in vivo for penicillin G plus gentamicin versus Enterococcus faecalis. The studies demonstrated that increasing concentrations of gentamicin caused an increased rate of bactericidal action and an increasingly prolonged PAE in vitro. The combination of penicillin and gentamicin, in addition to more rapid killing, exhibited a more prolonged PAE than did penicillin alone. However, unlike these in vitro findings, no PAE could be demonstrated in vivo in rats with experimental left-sided enterococcal endocarditis treated with penicillin plus gentamicin. This suggests that antibiotic vegetation levels should be maintained above the MIC throughout the dosing interval to prevent loss of efficacy as a result of bacterial regrowth.

Ciprofloxacin for the treatment of osteomyelitis: a review.

The authors review the use of ciprofloxacin, a new oral quinolone antibiotic, for the treatment of bone infections. The article discusses the spectrum of activity, pharmacokinetics, and toxicity of the quinolone agents. The authors also provide a detailed discussion of the efficacy of ciprofloxacin for osteomyelitis in animal studies and human trials.

Absence of a postantibiotic effect in experimental Pseudomonas endocarditis treated with imipenem, with or without gentamicin.

We found an in vitro postantibiotic effect (PAE) of 3-4 h for imipenem and of approximately 5 h for imipenem plus gentamicin against Pseudomonas aeruginosa. We therefore evaluated these antibiotics in a rat model of pseudomonas endocarditis. A rapid bactericidal effect was initially observed in vegetations from rats treated with imipenem alone or in combination with gentamicin. Bacterial counts rose rapidly, however, as soon as levels of imipenem in vegetations fell below the minimal inhibitory concentration (i.e., no PAE was demonstrated). Levels of gentamicin in vegetations were similar to those that had enhanced the bactericidal effect of imipenem and had resulted in a 5-h PAE in vitro. The presence in vitro of a PAE for imipenem, with or without gentamicin, does not necessarily predict its presence in vivo in pseudomonas endocarditis in the rat.

Nosocomial pneumonia.

Nosocomial pneumonia remains a challenging problem in critically ill patients in terms of both diagnosis and therapy. The clinical picture is often confusing; confounding factors such as congestive heart failure, ARDS, and interstitial lung disease may obscure the presence of pneumonia. Previous antimicrobial therapy or the presence of large numbers of colonizing organisms contribute to the difficulty of diagnosis. The use of sheathed fiberoptic bronchoscopy with quantitative culture and biopsy is probably the best initial invasive test when routine diagnostic methods fail; open lung biopsy remains the ultimate standard for diagnosis. Empiric therapy is often necessary and should be designed to treat organisms suspected of being the etiologic pathogens either on the basis of preliminary laboratory results (gram and acid-fast stains) or the clinical setting.

Relaxation time constant of isolated rabbit left ventricle.

Experiments were performed on isolated rabbit left ventricles. Controlled ejections during otherwise isovolumic contractions were studied. The time constant of relaxation was defined as the slope of the linear approximation of the ln(P)-t relation over a 40-ms period starting 20 ms after the minimum of the first time derivative of left ventricular pressure (dP/dt) of the isovolumic contraction. Variations in time of ejection, its amplitude, and velocity are applied independently. No direct effect of the variations in time and velocity of the ejection on the time constant of relaxation was found. This is in conflict with the findings of Hori et al. (Circ. Res. 55: 31-38, 1984). The difference is due to the influence of the recovery of pressure directly after the end of ejection in their study. This effect is present especially when ejection was timed to take place late in the contraction phase. The effect of the variation of the amplitude of the ejection on the time constant was similar to the effect of the end-diastolic pressure on the end-diastolic volume. It is concluded that the time constant of relaxation depends linearly on the same processes that are responsible for the height of the end-diastolic pressure.

beta-Lactamase production in experimental endocarditis due to aminoglycoside-resistant Streptococcus faecalis.

We used a beta-lactamase-producing (beta L+) strain of Streptococcus faecalis that also had high levels of resistance to all aminoglycosides to induce experimental endocarditis in rats. The rats were treated for five or 10 days with procaine penicillin, vancomycin, gentamicin, rifampin, or ciprofloxacin (alone or in various combinations), or with penicillin plus clavulanic acid. The levels of penicillin in serum and vegetations declined rapidly in the beta L+-infected rats treated with procaine penicillin alone, unlike the sustained levels of penicillin in either beta L- -infected rats treated with procaine penicillin or beta L+-infected rats treated with penicillin plus clavulanic acid. For the beta L+-infected rats, the enterococcal counts in vegetations were significantly reduced (greater than 3 log10 cfu/g) only by vancomycin and by penicillin plus clavulanic acid. The efficacy of the latter regimen probably resulted from the inhibition of penicillin inactivation by clavulanic acid in vegetations infected with the beta L+ strain. Our in vivo findings document the biologic significance of beta-lactamase production.

Clinical efficacy of ciprofloxacin therapy for gram-negative bacillary osteomyelitis.

The efficacy and toxicity of ciprofloxacin, an orally administered fluoroquinolone, were evaluated in 24 infections in 23 patients with osteomyelitis caused by aerobic gram-negative bacilli. The diagnosis was confirmed by surgical findings and the results of bone biopsy and culture of bone or deep soft tissue. The aerobic gram-negative bacilli were Pseudomonas aeruginosa (15 isolates), Serratia marcescens (five isolates), Escherichia coli (three isolates), Enterobacter species (three isolates), Proteus mirabilis (one isolate), Pseudomonas fluorescens (one isolate), and Klebsiella pneumoniae (one isolate). Minimal bactericidal concentrations (MBCs) were 1.56 micrograms/ml or less for all but one isolate. Nine infections were polymicrobial, involving aerobic gram-positive cocci or anaerobes in addition to aerobic gram-negative bacilli. Additional antibiotics to which the aerobic gram-negative bacilli were resistant were given when the additional organisms were resistant to ciprofloxacin. Patients received 750 mg of ciprofloxacin twice daily for a mean of 62 days. Peak serum levels of ciprofloxacin were at least threefold higher than the MBCs in 20 of 24 patients. Twenty of 22 infections in which a full course of therapy was completed were without evidence of active disease at one to 17 months posttreatment. A sternotomy wound infection relapsed after eight weeks of therapy with a newly resistant S. marcescens strain, and an infection of a compound fracture relapsed two months posttreatment with a still sensitive P. aeruginosa strain. Toxicity was minimal in most patients: eosinophilia (six patients), nausea (eight patients), mild elevation in transaminase levels (three patients), pruritus (one patient), diarrhea (two patients), thrush (two patients), rash (two patients), and mild leukopenia (one patient). Two additional patients had severe side effects (vertigo in one and acute renal failure in another) that required discontinuation of ciprofloxacin therapy. Overall, ciprofloxacin is a promising agent for the oral treatment of gram-negative bacillary osteomyelitis.