Frequency of small-colony variants and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus in cystic fibrosis patients

Background

Small-colony variants (SCVs) are a distinct phenotype of Staphylococcus aureus, known for their role in chronic, difficult to treat infections, including cystic fibrosis (CF) lung disease. The goal of this study was to characterize SCV MRSA infection in an adult and pediatric CF population and to identify antibiotic susceptibility patterns unique to SCV MRSA.

Large-artery stiffness contributes to the greater prevalence of systolic hypertension in elderly women

OBJECTIVES: To determine whether sex differences in large-artery stiffness contribute to the greater prevalence of systolic hypertension in elderly women than in elderly men. DESIGN: During a single visit arterial stiffness was assessed in the unmedicated state using four parameters. PARTICIPANTS: Three hundred seventy-four women with a mean age+/-standard deviation of 72+/-5 and 296 men aged 71+/-5 participated. SETTING: Hypertensive patients were recruited from general practice as part of the second Australian National Blood Pressure Study in Melbourne, Australia. MEASUREMENTS: Large-artery stiffness was assessed using multiple methodologies, including aortic arch stiffness (beta-index) using M-mode ultrasound and arterial compliance and augmentation index using noninvasive carotid pressure and aortic flow measurements. RESULTS: Women had greater carotid and brachial pulse pressure (PP) than men (P<.001), despite higher mean arterial pressure in men. Mean arterial compliance was lower in women (0.20+/-0.12 vs 0.28+/-0.16 mL/mmHg, P<.001) even after correction for aortic area, and aortic arch stiffness was higher (30+/-36 vs 23+/-22; P<.01). Consistent with both a stiffer proximal circulation and a shorter distance to reflection sites, women had higher augmentation index (38+/-11% vs 29+/-12%, P<.001). In multivariate analysis, sex was an independent determinant of all arterial stiffness indices. CONCLUSION: Independently of known confounders, elderly hypertensive women have stiffer large arteries, greater central wave reflection, and higher PP than elderly men. Stiffer large arteries likely contribute to the greater prevalence of systolic hypertension in elderly women and may partly explain the acceleration in postmenopausal cerebrovascular and cardiac complications.     

Induction of cross-reactive antibodies by immunization of healthy adults with types Ia and Ib group B streptococcal polysaccharide-tetanus toxoid conjugate vaccines

Types Ia and Ib group B streptococcal (GBS) capsular polysaccharides (PSs) are structural isomers but are antigenically distinct. Immunization of healthy adults with GBS type Ia PS-tetanus toxoid (Ia-TT) or Ib-TT glycoconjugate vaccines induced > or = 4-fold increases in specific immunoglobulin G to the heterologous PS in more than two-thirds of subjects. Ib-TT vaccine-induced IgG bound with substantially higher affinity to homologous (Ib) than to heterologous (Ia) PS and promoted opsonophagocytic killing of GBS type Ib but not type Ia organisms. The failure of the Ib-TT- and Ia-TT-induced human antibodies to kill bacteria of the cross-reactive serotype contrasts with the results of previous studies in animals. Inhibition enzyme-linked immunosorbent assays demonstrated that Ib-TT-induced IgG to the homologous PS bound mainly to native Ib PS, whereas the cross-reactive antibodies recognized both native and derivative PSs. These results indicate that GBS Ia and Ib PSs should be included in a multivalent conjugate vaccine to prevent GBS disease.     

Sympathetic nervous function in human heart as assessed by cardiac spillovers of dihydroxyphenylglycol and norepinephrine.

BACKGROUND. Measurement of cardiac norepinephrine spillover may indicate the amount of transmitter at neuroeffector sites but does not distinguish neuronal release or reuptake in determining this amount or provide information about other aspects of sympathetic function. This report examines how cardiac spillover of the norepinephrine metabolite dihydroxyphenylglycol (DHPG) provides additional distinct information about cardiac sympathetic function. METHODS AND RESULTS. Arterial and coronary venous blood samples were taken during cardiac catheterization and intravenous infusion of [3H]norepinephrine in 57 subjects. Subjects were given intravenous yohimbine or underwent mental stress, handgrip exercise, and cycling exercise to activate sympathetic nerves or were given intravenous desipramine to block norepinephrine reuptake. Cardiac DHPG spillover (601 +/- 41 pmol/min) was eightfold greater than norepinephrine spillover (78 +/- 10 pmol/min) at rest and increased during sympathetic activation by 65% of the increase of norepinephrine. This and the desipramine-sensitive cardiac production of [3H]-labeled DHPG from [3H]norepinephrine indicated that 10.5 times more endogenous norepinephrine is recaptured than escapes into plasma; that more than 90% of recaptured norepinephrine is sequestered into storage vesicles; and that under resting conditions, most cardiac spillover of DHPG and turnover of norepinephrine are from metabolism of transmitter leaking from vesicles; the latter process is independent of exocytotic transmitter release with a rate at rest over 100-fold that of norepinephrine spillover and over 10-fold that of norepinephrine reuptake. CONCLUSIONS. Cardiac spillover of DHPG provides information about processes close to or within sympathetic nerve endings that cannot be provided by measurements of norepinephrine spillover alone. This includes quantitative information about the role of neuronal uptake in terminating the actions of norepinephrine at neuroeffector sites and the importance of vesicular-axoplasmic exchange of norepinephrine as a dynamic process contributing to norepinephrine turnover.     

Increased norepinephrine spillover into the jugular veins in essential hypertension.

In essential hypertension sympathetic nerve firing is commonly increased. A central nervous system origin has been presumed but not tested directly. To estimate cerebral norepinephrine release in essential hypertension, spillover of norepinephrine into the cerebrovascular circulation was measured by isotope dilution, with high internal jugular venous sampling. Norepinephrine was released into the cerebrovascular circulation in both hypertensive patients and healthy volunteers and was present after administration of the ganglion blocker trimethaphan and in patients with sympathetic nervous failure, indicating that brain neurons and not cerebrovascular sympathetic nerves were the probable source. Although differing among hypertensive patients, norepinephrine spillover on average was higher in the hypertensive patients (153 +/- 41 pmol/min) than in healthy subjects (59 +/- 12 pmol/min; p less than 0.05), and was elevated in six of 17 patients, in whom the accompanying whole body norepinephrine spillover rate was higher than in the remaining 11 patients (p less than 0.01). To test for a possible link between brain norepinephrine release and human sympathetic nervous function, the effect of the tricyclic antidepressant desipramine (0.3 mg/kg i.v.) on both brain and whole body norepinephrine spillover was measured in healthy volunteers. Desipramine lowered the cerebrovascular spillover of norepinephrine, its precursor dihydroxyphenylalanine, and its metabolite dihydroxyphenylglycol by 50-80% and produced a mean fall of 35% in whole body norepinephrine spillover. One interpretation of these results is that human sympathetic nerve firing is dependent on norepinephrine release within the brain and that increased cerebral norepinephrine release may possibly be present in some patients with essential hypertension, underlying their higher sympathetic nerve firing rates.     

The impact of blood cultures on antibiotic therapy in pneumococcal pneumonia

INTRODUCTION: The cost-effectiveness of blood cultures in community-acquired pneumonia (CAP) has been questioned. Although penicillin-resistant Streptococcus pneumoniae is an increasing problem, penicillin therapy, where appropriate, reduces cost and may reduce antibiotic resistance. Blood cultures, however, can only reduce cost if physicians are prepared to alter therapy based on the results. We reviewed our experience to determine how often physicians changed management based on blood culture results positive for S pneumoniae. METHODS: Retrospective chart review was performed of all CAP admissions between January 1996 and December 1998 with blood culture results positive for S pneumoniae. RESULTS: Seventy-four patients out of 1,805 patients admitted with CAP during this period had pneumococcemia. Penicillin resistance was identified in 15 cases (20.3%; high grade in 4 cases) with cephalosporin resistance in 4 of these cases (1 high grade). Fifty-one patients had initial empiric therapy with a third-generation cephalosporin, and 58 patients had empiric coverage of atypical organisms; no patient received empiric penicillin therapy. Blood culture results altered management in 31 patients (41.9%), but in only 2 cases was this due to antibiotic resistance. Fifty-one patients without penicillin allergy grew penicillin-sensitive pneumococci; only 11 patients (21.6%) were changed to penicillin therapy. Thirteen of 35 patients (37.1%) who were given an additional antibiotic for atypical coverage had this antibiotic ceased. CONCLUSION: Despite evidence of penicillin-sensitive pneumococcal CAP, physicians were reluctant to narrow antibiotic therapy, potentially adding to treatment cost and reducing the impact of blood culture results on management. The impact of penicillin resistance was reduced by the usual empiric choice of a third-generation cephalosporin. While positive blood culture results can clearly be useful in the management of patients with CAP, their cost-effectiveness needs to be assessed in prospective clinical trials.     

Duration and reinstatement of myocardial protection against infarction by ischemic preconditioning in open chest dogs

These studies were undertaken to determine the duration of protection against myocardial infarction provided by ischemic preconditioning in the canine heart, and to learn if cardioprotection can be restored by another preconditioning stimulus when the initial effect is lost. Control and four preconditioning groups of anesthetized, open-chest dogs were compared. All underwent a test 60 min episode of ischemia, induced by occlusion of the anterior descending (LAD) artery, followed by 3 h of reperfusion. Preconditioning was induced by one 10 min LAD occlusion, followed by either 10 min, 2, 3, or 5 h of reperfusion. In order to test whether preconditioning could be reinstated, another group of dogs with preconditioning plus 3 h reperfusion underwent a second 10 min preconditioning stimulus with 10 min reperfusion before the 60 min test-occlusion. Infarct size (as percent of area-at-risk) was analyzed (using analysis of covariance) with respect to coronary collateral blood flow measured with radioactive microspheres. Infarct size was limited markedly by preconditioning (23+/-6 v 6+/-2%, P<0.05) but the protective effect was dissipated partially after 2 h reperfusion and was dissipated completely after 3 h reperfusion (20+/-4%, non-significant v Control and significant P<0.05 v preconditioning). Protection was restored in three of six dogs with preconditioning +5 h reperfusion, suggesting that the second window of protection appears early in some canine hearts. When preconditioning was repeated after 3 h reperfusion, cardioprotection was reinstated fully (7+/-2%, P<0.05 v Control and NS v preconditioning). The results show that maximal preconditioning cardioprotection is present in the dog heart after 10 min of reperfusion and is dissipated totally following 3 h of reperfusion. However, a second preconditioning stimulus of 10 min of ischemia followed by 10 min of reperfusion to the dissipated preconditioned heart reinstates full preconditioning. Thus, this model provides a system to test for theoretical causes of the preconditioned state. Final mediators should be present when preconditioning is present and absent when preconditioning is dissipated. It is noteworthy that a second window of protection appeared in 50% of dogs when the period of reperfusion was extended to 5 h.     

Time-course of the antihypertensive and autonomic effects of regular endurance exercise in human subjects

To assess the role of different factors on the long-term antihypertensive effect of regular exercise we examined the time course of changes in haemodynamics, oxygen consumption and plasma noradrenaline in 10 normal healthy subjects. For 12 weeks, subjects performed alternating months of training and detraining in a random order. Training involved 40 min of bicycle exercise three times per week at 60-70% of maximum work. Steady-state changes at the end of 1 month's exercise were: (1) falls in resting blood pressure when supine and erect by 8/5 and 10/6 mmHg, respectively (P less than 0.01); (2) a reduction in the total peripheral resistance index of 14%; (3) an increase in maximum oxygen consumption of 14% (P less than 0.005); and (4) a fall in plasma noradrenaline of 21% (P less than 0.05). A significant fall in blood pressure occurred at the third training bout (P less than 0.005), at the beginning of the second week, and no further reduction occurred beyond the fourth bout of exercise. The reduction in plasma noradrenaline concentration was confined to the second half of the month in which exercise took place and lagged behind the blood pressure changes. There were significant differences between the rates of the initial fall of blood pressure and noradrenaline, and the times taken for the maximum changes to occur (P less than 0.05). During detraining, blood pressure remained low for 1-2 weeks after cessation of exercise, as did plasma noradrenaline. Both then rose gradually towards the initial sedentary levels.(ABSTRACT TRUNCATED AT 250 WORDS)