Combination of amphotericin B with flucytosine is active in vitro against flucytosine-resistant isolates of Cryptococcus neoformans

The combination of flucytosine and amphotericin B was tested against 10 flucytosine-resistant isolates of Cryptococcus neoformans by checkerboard, killing curves, and Etest. Although differences were observed depending on the technique used, antagonism was never observed. The synergistic interaction was related to the mechanism of flucytosine resistance of the isolates.     

Emergency preservation and resuscitation improve survival after 15 minutes of normovolemic cardiac arrest in pigs

OBJECTIVE: Outcome after prolonged normovolemic cardiac arrest is poor, and new resuscitation strategies have to be found. We hypothesized that the induction of deep hypothermia for emergency preservation and resuscitation (EPR) during prolonged cardiac arrest, before the start of reperfusion, will mitigate the deleterious cascades leading to neuronal death and will thus improve outcome. DESIGN: Prospective experimental study. SETTING: University research laboratory. SUBJECTS: Thirteen pigs, Large White breed (27-37 kg). INTERVENTIONS: After 15 mins of ventricular fibrillation, pigs were subjected to 1) EPR (n = 6), 20 mins of hypothermic stasis induced with a cold saline aortic flush; or 2) 20 mins of conventional resuscitation (n = 7). Then cardiopulmonary bypass was initiated in both groups, followed by defibrillation. Controlled ventilation and mild hypothermia were continued for 20 hrs; survival was for 9 days. For neurologic evaluation, neurologic deficit score (100% = brain dead, 0-10% = normal), overall performance category (1 = normal, 5 = dead or brain dead), and brain histologic damage score were used. MEASUREMENTS AND MAIN RESULTS: In the EPR group, brain temperature decreased from 38.5 degrees C +/- 0.2 degrees C to 16.7 degrees C +/- 2.5 degrees C within 235 +/- 27 secs. Five animals achieved restoration of spontaneous circulation and survived to 9 days: two pigs with overall performance category 2 and three pigs with overall performance category 3. Their neurologic deficit score was 45% (interquartile range 35, 50) and histologic damage score was 142 (interquartile range 109, 159). In the control group, four pigs achieved restoration of spontaneous circulation: one survived to 9 days with overall performance category 3, neurologic deficit score 45%, and histologic damage score 226 (restoration of spontaneous circulation, p = .6; survival, p = .03; overall performance category, p = .02). CONCLUSIONS: EPR is feasible in an experimental pig model and improves survival after prolonged cardiac arrest in pigs. Further experimental studies are needed before this concept can be brought into clinical practice.     

New echocardiographic applications for assessing global left ventricular diastolic function

A number of promising and highly technological echocardiographic imaging tools have recently been introduced to assess left ventricular diastolic function (i.e., the capacity of the ventricle to relax and fill). They permit quantification of distinct features of intraventricular blood flow velocity and pressure fields and myocardial tissue velocities. However, accurate interpretation of the new images and clinical indices is still cumbersome, as basic knowledge about intraventricular hemodynamics and ventricular wall mechanics is often insufficient. This review article provides a comprehensive and original overview of the hemodynamical and mechanical events that occur during diastole and discusses how this new information can be used in the clinical and research setting to evaluate diastolic function in the healthy and the diseased heart. It furthermore aims to explain the underpinnings of the techniques in such a way that the underlying biomechanical concepts (fluid dynamics and wall mechanics) become less obscure to cardiologists and echocardiographers and such that the biomedical engineers are given some insights into the avalanche of diastolic performance indices that currently exist.     

Evaluation of emergency medical dispatch in out-of-hospital cardiac arrest in Taipei

INTRODUCTION: Emergency medical dispatchers are the entry points to the emergency medical services (EMS). The overall performances of the dispatchers are imperative determinants of the emergency medical services dispatching system. There is little data on the cultural and language impacts on emergency medical dispatch. OBJECTIVE: This study examined the emotional content and cooperation score (ECCS) among Mandarin Chinese speaking callers for cardiac arrests, and evaluated the performances of emergency medical services dispatching system in Taipei. METHODS: This retrospective, observational study examined dispatching audio recordings obtained from the Taipei City Fire Department Dispatching Center between January 2004 to April 2004. The tapes of call relating to adult (age >or=18 years), non-traumatic cases with a presumed or field diagnosis of out-of-hospital cardiac arrest (OHCA) underwent systemic review. The caller's ECCS and the dispatcher's performances, including interview skills, provision of telephone-assisted cardiopulmonary resuscitation (T-CPR), and dispatcher's ability to identify OHCA were examined. Interrater reliability for determining ECCS and interview skills were assessed using kappa statistic. RESULTS: A total of 199 audio recordings were reviewed. A mean ECCS of 1.42+/-0.64 (95% CI: 1.33-1.51) demonstrated that most callers were emotionally stable and cooperative when calling for help, even when facing cardiac arrest patients. There was a good association between ECCS and the sex of the callers (male 1.32 versus female 1.49; p<0.05). In 82% of interviews, the interview skills of the dispatchers was high (4 or 5 points); while in one fifth the interview skills were suboptimal. About one third of the cases were provided with T-CPR by the dispatchers. The sensitivity and positive predictive value (PPV) for predicting OHCA by dispatchers were 96.9% and 97.9%, respectively. A kappa value of 0.65 and 0.68 were obtained for the interrater reliability of ECCS and interview skills. CONCLUSION: Most callers were found to be emotional stable and cooperative with dispatcher's interrogations when calling for cardiac arrest victims in this Mandarin speaking population. The dispatchers have shown satisfactory interview skills in approaching emergency calls and a good ability to identify OHCA. There is a low rate of T-CPR offered to the callers in the investigation. Efforts should be made to address the deficiencies in order to maximise the function of the EMS.     

Emergence of a Streptococcus pneumoniae isolate resistant to streptogramins by mutation in ribosomal protein L22 during pristinamycin therapy of pneumococcal pneumonia

OBJECTIVES: The aim of this study was to characterize the mechanism of resistance to macrolides and streptogramins of a Streptococcus pneumoniae strain isolated from blood cultures in an 80-year-old patient suffering from severe pneumonia unsuccessfully treated with pristinamycin. METHODS: Resistance genes erm(B) and mef(A) were searched for by PCR. Portions of genes for domains V and II of the 23S rRNA (rrl) and genes for ribosomal proteins L4 (rplD) and L22 (rplV) were amplified by PCR from total genomic DNA and sequenced. RESULTS: Resistance genes erm(B) and mef(A) were not detected. Only mutation in the rplV gene encoding ribosomal protein L22 was detected. The strain contained a six amino acid insertion ((107)KRTAHI(108)) in the C-terminus of the ribosomal protein L22. CONCLUSIONS: This is the first report of emergence of a pneumococcus resistant to streptogramins by mutation in ribosomal protein L22 during treatment with pristinamycin.     

Antisense peptide-phosphorodiamidate morpholino oligomer conjugate: dose-response in mice infected with Escherichia coli

OBJECTIVES: Phosphorodiamidate morpholino oligomers (PMOs) are DNA analogues that inhibit translation by an antisense mechanism. Membrane-penetrating peptides attached to PMOs increase PMO efficacy by enhancing penetration through bacterial membranes. The objectives of these experiments are to demonstrate gene-specific efficacy and establish a dose-response relationship of a peptide-PMO conjugate. METHODS: An 11-base PMO (AcpP) targeted at acpP (an essential gene) of Escherichia coli was synthesized and conjugated with the cell-penetrating peptide RFFRFFRFFRXB (X is 6-aminohexanoic acid and B is beta-alanine). Mice were infected by intraperitoneal (i.p.) injection with K-12 E. coli W3110, and treated i.p. at 15 min and 12 h post-infection with various amounts of AcpP peptide-PMO conjugate, AcpP PMO without attached peptide, scrambled base sequence PMOs or ampicillin. A strain (LT1) of E. coli was constructed by replacing acpP with an allele that has four wobble base substitutions in the region targeted by the PMO. RESULTS: Twelve hours after a single treatment, 30 microg of AcpP peptide-PMO or 3 mg of AcpP PMO reduced bacteraemia by 3 orders of magnitude compared with treatment with water. Neither scrambled base sequence PMO controls nor 30 microg of ampicillin reduced bacteraemia. Two treatments with 30 microg of AcpP peptide-PMO reduced cfu significantly more than four treatments with 15 microg at 15 min, 4, 8 and 12 h. Mice treated with doses of AcpP peptide-PMO > 30 microg showed further reductions in plasma cfu. Survival 48 h after treatment with 2 x 30 microg (3 mg/kg) of AcpP peptide-PMO or 2 x 3 mg (300 mg/kg) of AcpP PMO was 100%, compared with 20% for mice treated with water or scrambled base sequence PMO controls. However, survival was reduced to 75% and 0% for mice treated with 2 x 300 microg and 2 x 1 mg of AcpP peptide-PMO, respectively. A conjugate made from the D-isomeric form of each amino acid was less effective than the L-amino acid equivalent, and required 2 x 300 microg treatments for significant reduction in bacteria and survival. Mice infected with LT1 and treated with AcpP peptide-PMO did not survive and had the same amount of bacteria in the blood as mice treated with water, whereas those treated with 2 x 100 microg of AcpPmut4 peptide-PMO (complementary to the mutated allele) survived, and had a 3 orders of magnitude reduction in bacteria in the blood at 24 h post-infection. CONCLUSIONS: Both AcpP peptide-PMO and AcpP PMO significantly reduced bacteraemia and promoted survival of mice infected with E. coli W3110. The conjugate was about 50-100 times more potent than the PMO without attached peptide. The L-isomeric peptide-PMO was 10 times more potent than the D-isomeric equivalent. The conjugate apparently was toxic at doses > or = 2 x 300 microg/mouse (30 mg/kg). PMOs produced a sequence-specific antibiotic effect and the conjugate had a therapeutic index (toxic dose/effective dose) approximately equal to 10 in a mouse model of infection.     

Gesichtsästhetik Teil 1: Die Bedeutung der Symmetrieebene des Gesichts

When humans observe a face, the eyes, mouth and nose regions are the preferred targets of the centre of gaze, with the outlines of eye position recordings approximating a triangle with vertices located in the centre of the eyes and mouth [31]. We studied the significance of cutaneous asymmetries inside and outside the Yarbus triangle on the basis of the assessment of digitally-manipulated images by 201 independent judges. We show that certain facial variations (such as naevi) are more attractive when asymmetrical than symmetrical (p<?0,001). They appear more attractive when located laterally rather than medially, particularly so when located outside the Yarbus triangle as compared to inside it (p<?0,001). The significance of facial symmetry increases significantly when approaching the Yarbus triangle or the midline, respectively.