ACE inhibition and protection from doxorubicin-induced cardiotoxicity in the rat

The angiotensin converting enzyme inhibitor zofenopril has been shown to possess cardioprotective effects toward myocardial damage induced by chronic doxorubicin treatment in the rat. In the present study we have investigated the relationship between cardioprotection exerted by 2 angiotensin converting enzyme inhibitors (zofenopril and lisinopril) and degree of inhibition of cardiac versus serum angiotensin converting enzyme. Both zofenopril and lisinopril produced a dose-dependent inhibition of serum and cardiac angiotensin converting enzyme in rats (0.1, 1 or 10 mg/kg/day in the diet for 1 week). However, zofenopril at 0.1 mg/kg/day showed a significantly (P < 0.05) greater inhibition of angiotensin converting enzyme in the myocardium than in the serum (Δ about 20%). Using dose levels (0.1 mg/kg/day and 10 mg/kg/day) which inhibits partially (about 50%) or almost totally (about 80%) serum angiotensin converting enzyme, we evaluated the effects of zofenopril and lisinopril in preventing cardiac alterations (QαT prolongation) induced by chronic treatment with doxorubicin (1.5 mg/kg q7dx5 i.v.). Zofenopril, at a dose level (0.1 mg/kg/day) that did not affect haemodynamics and only partially inhibits serum angiotensin converting enzyme activity, almost totally prevent the QαT lengthening induced by doxorubicin, whereas lisinopril was ineffective at this dose level. At the higher dose level (10 mg/kg/day), both angiotensin converting enzyme inhibitors totally prevented the electrocardiographic alteration induced by chronic doxorubicin administration. Cardioprotection exerted by zofenopril at a dose level that partially inhibits serum angiotensin converting enzyme without affecting haemodynamics, suggests that inhibition of cardiac angiotensin converting enzyme and additional cardioprotective mechanism(s) may have a role in its ability to prevent myocardial damages in the rat subjected to chronic anthracycline treatment.     

Repetitive nerve stimulation in myasthenia gravis—relative sensitivity of different muscles

Objective: To correlate repetitive nerve stimulation (RNS) decrement in different muscles with the predominant clinical presentation in myasthenia gravis (MG), and to study single fibre EMG (SFEMG) sensitivity in ocular MG.Methods: Sixty-nine, untreated, consecutive patients suspected for MG were observed prospectively for a minimum of 6 months. Those who improved on medical treatment were diagnosed as MG. The others, in whom the neurophysiological studies were normal and that did not improve on medical treatment served as a control group, from which normative data for RNS and SFEMG was obtained. The MG patients were further classified in 3 subgroups according to the predominant clinical presentation: group I (ocular); group b (bulbar); and group a (axial). We performed RNS in nasalis, trapezius, anconeus, and abductor digiti minimi. All patients with ocular MG underwent jitter determination of the orbicularis oculi muscle.Results: Thirty-seven patients were diagnosed as MG (group I, 15; group b, 13; group a, 9). In group I, RNS was abnormal in 33% of the patients. RNS studies disclosed at least one abnormal muscle response in every patient in groups a and b. Trapezius was significantly more sensitive in group a, and anconeus and nasalis in group b (P<0.01). Jitter was abnormal in all patients in group I, and the most sensitive parameter was an increased number of unstable pairs, 100%.Conclusions: Based on these observations, we recommend that a shoulder muscle, as the trapezius, should be studied first in the limb-axial presentation of MG, and the anconeus–nasalis muscles in predominant bulbar MG. In ocular MG, RNS is not sensitive and jitter should be performed in facial muscles.Significance: This paper shows the unequal sensitivity of several muscles to RNS in different forms of MG.     

Pharmacology of LR-B/081, a new highly potent, selective and orally active, nonpeptide angiotensin II AT1 receptor antagonist.

1. The pharmacological profile of LR-B/081, (methyl 2-[[4-butyl-2-methyl- 6-oxo-5-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1(6H)- pyrimidinyl]methyl]-3-thiophenecarboxylate), a novel antagonist at the angiotensin II (AII) AT1-receptor, was studied in vitro and in vivo. 2. In rabbit aortic strips incubated with LR-B/081 (1-1,000 nM), the concentration-response curve to AII was displaced to the right in a nonparallel fashion and the maximal contraction was progressively reduced, indicating that the compound is an insurmountable antagonist in this preparation (apparent pKB = 9.50 +/- 0.23). However, the interaction of LR-B/081 with AII receptors was found to be reversible, since the maximal response to AII was restored by coincubation with losartan, a surmountable AII AT1-antagonist. Contractions elicited by KCl or phenylephrine were not affected by 10 microM LR-B/081. 3. In rat isolated perfused kidney, LR-B/081 and losartan antagonized the AII-induced vasoconstriction [IC50 (95% confidence limits) = 17(13-24) and 39(32-54) nM, respectively]. The LR-B/081 antagonism was incompletely reversed by excess AII, while losartan was fully displaced. The IC50 values of LR-B/081 and losartan obtained against vasoconstriction induced by endothelin-1 and noradrenaline were two orders of magnitude higher. 4. In pithed rats, the intravenous administration of LR-B/081 (0.2-2 mumol kg-1) dose-dependently shifted to the right in a nonparallel fashion the dose-pressor response curve to AII. The maximal pressor response to AII was reduced by LR-B/081 in a dose-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genetic education,knowledge and experiences between nurses and physicians in primary care in Brazil: A cross‐sectional study

Recent advances in genomics and related technologies have the potential to improve health care throughout the world. In this cross‐sectional study, we examine genetics education, knowledge, and genetics‐related experiences among the nurses and physicians who provide primary care in a Brazilian city. Fifty‐four healthcare professionals from family health units participated in the study (response rate: 90%). Data were collected using a structured 36‐item questionnaire divided into five axes: sociodemographic data and academic background; genetics education; genetics knowledge; genetics‐related experiences in family practice; and knowledge regarding the National Policy for Comprehensive Care in Clinical Genetics in the Unified Health System. Although most participants (85.2%) acknowledged receiving some genetic content during their undergraduate education, the majority (77.8%) advised that they did not feel prepared to deliver genomics‐based health care in primary care. The results suggest that nurses and physicians often lack the knowledge to provide genomics‐based health care in primary care. Therefore, continuing education in genetics/genomics should be provided to primary healthcare professionals in order to enhance family practice and compliance with national policies.     

Intra- and Interrater Reliability and Concurrent Validity of a New Tool for Assessment of Breast Cancer–Related Lymphedema of the Upper Extremity

Objective

The goal of this study was to develop and assess intra- and interrater reliability and validity of a clinical evaluation tool for breast cancer–related lymphedema, for use in the context of outcome evaluation in clinical trials.

Prevalence of Single Mutations in Topoisomerase Type II Genes among Levofloxacin-Susceptible Clinical Strains of Streptococcus pneumoniae Isolated in the United States in 1992 to 1996 and 1999 to 2000

Levofloxacin resistance in Streptococcus pneumoniae is rare, requiring at least two mutations in the quinolone resistance-determining region (QRDR) of topoisomerase IV and DNA gyrase. The prevalence of single QRDR mutations in these genes is unknown. Of 9,438 levofloxacin-susceptible pneumococci from the TRUST 4 surveillance study (1999-2000), 528 strains (MICs of 0.5 to 2.0 microg/ml) were selected for analysis. For comparison, 214 levofloxacin-susceptible strains (MICs of 0.5 to 1 microg/ml) isolated between 1992 and 1996 were analyzed. Oligonucleotide probe assay and DNA sequencing were used to detect QRDR mutations leading to changes at Ser79 and Asp83 in ParC, Ser81 in GyrA, and Asp435 in ParE, the most frequently found substitutions among levofloxacin-resistant strains. Among the 1992 to 1996 isolates only one strain (levofloxacin MIC, 1 microg/ml) had a mutation (Ser79 to Phe in ParC). No single mutations were found among 270 TRUST 4 strains with levofloxacin MICs of 0.5 microg/ml. Among 244 strains for which levofloxacin MICs were 1 microg/ml, 15 strains (6.1%) had a parC mutation and 3 strains (1.2%) had a parE mutation. Of 14 strains for which levofloxacin MICs were 2 microg/ml, 10 strains (71%) had a parC mutation; no parE mutations were found. No gyrA mutations were detected. It was estimated that 4.5% of the 9,438 levofloxacin-susceptible TRUST 4 isolates (MICs, < or =0.06 to 2 microg/ml) had a single parC or parE QRDR mutation. Although there has been an increase in the prevalence of single-step mutants, the increase may have been overestimated due in part to differences in geographical distribution for the two sets of isolates.     

Efficacy and safety of late-start Corifollitropin-alfa administration for controlled ovarian hyperstimulation in IVF: a cohort,case–control study

ObjectiveTo investigate efficacy and safety of a controlled ovarian stimulation (COS) protocol in which a single dose of Corifollitropin-alfa (CFα) was administered on day 4 of a GnRH-antagonist cycle.DesignCohort case–control study.SettingUniversity Hospital.PatientsOne hundred twenty-two normally cycling women expected to be normal responders to COS.InterventionsIn 61 patients, CFα (100–150 μg) was injected subcutaneously on day 4 of a spontaneous menstrual cycle; a GnRH-antagonist was added from day 8 (fixed protocol; 0.25 mg/day). If needed to complete follicular maturation, recombinant FSH (rFSH) daily injections (150/200 IU/day) were given from day 11. A control group of 61 matched women was stimulated with daily subcutaneous injections of rFSH (100–150 U/day) from day 4 of the cycle, and received GnRH-antagonist (0.25 mg/day) from day 8. IVF or ICSI was performed according to the sperm characteristics, and 1–2 embryos were transferred in utero under US guidance on day 2.ResultsNo cycle was cancelled and the mean number of retrieved COCs was comparable in patients and controls. About 60 % of CF-alfa treated women had no need of daily rFSH addition, and the mean number of injections/cycle was significantly lower in the CF-alfa group than in controls (p < 0.05). The ongoing PR/transfer was 36.8 % in CF-alfa group and 37.5 % in controls. No patient developed severe OHSS, and the incidence of moderate OHSS was similar in cases and controls.ConclusionsCFα may be started on day 4 of the cycle obtaining results comparable to those of a COS using day 4-start daily rFSH, with significantly less injections and a similar risk of OHSS.     

Cardiovascular imaging in aortic disease. Multimodality approach in clinical practice

IntroductionIn the last decade, remarkable advances have been made in noninvasive imaging of aortic diseases. The aim of this article was to provide a comprehensive review of these imaging modalities. Echocardiography plays an important role in the diagnosis and follow-up of aortic diseases. Transthoracic echocardiography (TTE) permits adequate assessment of several aortic segments, particularly aortic root and proximal ascending aorta. Transoesophageal echocardiography (TEE) overcomes the limitations of TTE in thoracic aorta assessment. TTE and TEE should be used in a complementary manner. Although TEE is the technique of choice in the diagnosis of aortic dissection, TTE may be used as the initial modality in the emergency setting. Intimal flap in proximal ascending aorta, pericardial effusion/tamponade and left ventricular function can be easily visualised by TTE. TEE information (entry tear location, mechanisms and severity of aortic regurgitation and true lumen compression) is essential for selecting and monitoring surgical and endovascular treatment and detecting possible complications. Computed tomography has the advantage of providing optimum morphological information of the entire aorta and the accuracy of size measurements. Magnetic resonance imaging offers good morphological and dynamic information on the aorta without radiation, although in clinical practice its availability is lower.ConclusionsThe considerable advances in imaging techniques have greatly increased our understanding of aortic diseases. Not only clinical presentation and required information, but also local availability of imaging equipment and staff expertise in this field, should be considered to indicate echocardiography, computed tomography or magnetic resonance, in the assessment of different aortic diseases and their circumstances.