Impact of pharmaceutical intervention on quality of life and coping strategies in patients with haematological malignancies.

OBJECTIVES: We conducted a prospective study approved by the local ethics committee to determine the impact of a pharmaceutical intervention (PI) on pain, fatigue, quality of life (QoL) and coping strategies in patients with HMs starting chemotherapy sessions. MATERIAL AND METHODS: Patients received either usual care (UC)+PI (PI group) or UC alone (UC group). They had to complete 2 questionnaires, QLQ-C30 and MAC 21, at 3 different time points: before starting the 1st chemotherapy session (T1), during the intercure (T2) and the day before starting the 2nd chemotherapy session (T3). To determine predictive factors of pain, fatigue, QoL and coping scores at T3, a multivariate ANOVA was used. QoL and coping scores were analysed longitudinally using a linear mixed model. RESULTS: Sixty-eight patients were included in the PI (n=34) or UC groups (n=34). Ninety-two percent of the patients returned all the questionnaires. At inclusion, QoL was significantly better in the PI group (P=0.047). At T3, the group had no influence on pain, fatigue, nor coping scores but a trend towards a better QoL was observed in the PI group (P=0.090). Longitudinally, the PI group did not present significantly better scores on pain, fatigue but both a trend toward better Qol scores and lower anxious preoccupations scores. CONCLUSION: A PI at the beginning of chemotherapy sessions did not have any significant impact on pain and fatigue but a trend towards better Qol scores and lower anxious preoccupations scores.

Molecular investigation of resistance to the antituberculous drug ethionamide in multidrug-resistant clinical isolates of Mycobacterium tuberculosis.

Ethionamide (ETH) needs to be activated by the mono-oxygenase EthA, which is regulated by EthR, in order to be active against Mycobacterium tuberculosis. The activated drug targets the enzyme InhA, which is involved in cell wall biosynthesis. Resistance to ETH has been reported to result from various mechanisms, including mutations altering EthA/EthR, InhA and its promoter, the NADH dehydrogenase encoded by ndh, and the MshA enzyme, involved in mycothiol biosynthesis. We searched for such mutations in 87 clinical isolates: 47 ETH-resistant (ETH(r)) isolates, 24 ETH-susceptible (ETH(s)) isolates, and 16 isolates susceptible to ETH but displaying an intermediate proportion of resistant cells (ETH(Sip); defined as ≥1% but <10% resistant cells). In 81% (38/47) of the ETH(r) isolates, we found mutations in ethA, ethR, or inhA or its promoter, which mostly corresponded to new alterations in ethA and ethR. The 9 ETH(r) isolates without a mutation in these three genes (9/47, 19%) had no mutation in ndh, and a single isolate had a mutation in mshA. Of the 16 ETH(Sip) isolates, 7 had a mutation in ethA, 8 had no detectable mutation, and 1 had a mutation in mshA. Finally, of the 24 ETH(s) isolates, 23 had no mutation in the studied genes and 1 displayed a yet unknown mutation in the inhA promoter. Globally, the mechanism of resistance to ETH remained unknown for 19% of the ETH(r) isolates, highlighting the complexity of the mechanisms of ETH resistance in M. tuberculosis.

Outbreak of tuberculosis in a migrants' shelter, Paris, France, 2002.

SETTING: An overcrowded 362-bed migrants' shelter in Paris, France. OBJECTIVES: To investigate an outbreak of tuberculosis (TB), to identify a common source of contamination and to prevent further transmission. METHODS: The outbreak was identified by radiographic screening and an active search for undeclared hospital treated cases, completed by strain phenotyping and a search for contact cases. RESULTS: Between October 2001 and October 2002, 56 cases of active TB were identified, 30 by radiological screening and 20 by contacting neighbouring hospitals. All cases involved men, with a median age of 30 years. Pulmonary involvement was present in 54% of cases, and nine patients were sputum smear-positive. Thirty-four of the 37 phenotyped strains clustered together. CONCLUSION: The grouping of the cases in time and place, the large number of cases with early-stage disease and the identical RFLP banding patterns of most of the isolates indicate that this outbreak results from transmission that occurred in France. This report underlines the need for public health departments in industrialised countries to maintain effective anti-tuberculosis control programmes.

Pulsed Doppler flow characteristics of ductus arteriosus in infants with associated congenital anomalies of the heart or great arteries.

Pulsed Doppler echocardiography (PDE) from the suprasternal approach was used to assess flow characteristics of ductus arteriosus (DA) in 145 infants (aged 1 day to 6 months) with major congenital heart disease. Direct ductal Doppler interrogation was possible in 138 patients and serial studies before and after medical treatment were performed in 28 infants. According to pulmonary artery pressure and associated heart lesions, 3 ductal shunting patterns were identified. An isolated left-to-right shunt, observed in isolated DA or in right ventricular outflow tract obstruction, was characterized by a continuous flow with a peak velocity in late systole. An isolated right-to-left shunt, observed in persistent fetal circulation and aortic arch abnormalities, was characterized by a continuous flow with a peak velocity in early systole. In patients with a bidirectional ductal shunt, the right-to-left shunt always occurred in systole and the left-to-right shunt began in late systole and extended into diastole. A systolic right-to-left shunt always corresponded to the presence of significant pulmonary hypertension. Ductal flow changes could be documented after prostaglandin E1 therapy in patients with ductus-dependent heart disease or after tolazoline therapy in patients with persistent fetal circulation. Thus, PDE with direct ductal Doppler interrogation is an important complement to the echocardiographic evaluation of DA. It is a safe noninvasive approach to ductal shunt and permits convenient evaluation of the effects of drugs on pulmonary artery resistance (tolazoline) and ductal patency (prostaglandin E1).

A new Doppler method of assessing left ventricular ejection force in chronic congestive heart failure.

A noninvasive method using Doppler echocardiography was developed to determine the force exerted by the left ventricle in accelerating the blood into the aorta. The value of this new Doppler ejection index in the assessment of left ventricular (LV) performance was tested in 36 patients with chronic congestive heart disease undergoing cardiac catheterization and in 11 age-matched normal control subjects. The 36 patients were subgrouped into 3 groups based on angiographic ejection fraction (LV ejection fraction greater than 60, 41 to 60 and less than or equal to 40%). According to Newton's second law of motion (force = mass X acceleration), the LV ejection force was derived from the product of the mass of blood ejected during the acceleration time with the mean acceleration undergone during that time. In patients with LV ejection fraction less than or equal to 40%, LV ejection force, peak aortic velocity and mean acceleration were severely depressed when compared with the other groups (p less than 0.001). In patients with LV ejection fraction of 41 to 60%, LV ejection force was significantly reduced (22 +/- 3 kdynes) when compared with normal subjects (29 +/- 5 kdynes, p = 0.002) and with patients with LV ejection fraction greater than 60% (29 +/- 7 kdynes, p = 0.009); peak velocity and mean acceleration did not differ between these 3 groups. The LV ejection force showed a good linear correlation with LV ejection fraction (r = 0.86) and a better power fit (r = 0.91). Peak aortic blood velocity and mean acceleration showed less good linear correlations with LV ejection fraction (r = 0.73 and r = 0.66, respectively). The mass of blood ejected during the acceleration time also showed a weak linear correlation with LV ejection fraction (r = 0.64). An LV ejection force less than 20 kdynes was associated with a depressed LV performance (LV ejection fraction less than 50%) with 91% sensitivity and 90% specificity. Thus, these findings suggest that LV ejection force is a new Doppler ejection phase index that appears to be more accurate than peak aortic blood velocity and mean acceleration for the assessment of systolic LV function.

A simplified normalized ejection phase index measured by Doppler echocardiography for the assessment of left ventricular performance.

Although useful for the assessment of directional changes in contractility in individual patients, resting peak aortic blood velocity is of limited value for differentiating among patients with different levels of basal cardiac function. A dimensional analysis based on fluid dynamics shows that peak aortic blood velocity is not only generated by the contracting myocardium but also reflects the convective acceleration of blood from the left ventricle to the aorta. The reduction of cross-sectional area from the midleft ventricle to the aorta at the time of peak aortic blood velocity generates the convective acceleration. Accordingly, a higher convective acceleration due to left ventricular (LV) enlargement as observed in cardiomyopathy may explain why peak aortic blood velocity can be maintained as normal although myocardial contractility is depressed. This study tested the hypothesis that peak aortic blood velocity normalized by the ratio of midleft ventricle to aortic cross-sectional areas might provide a reliable index of LV performance. Nine normal control subjects and 25 patients undergoing catheterization were studied by M-mode, 2-dimensional and Doppler echocardiography. The normalized peak velocity measured noninvasively showed a high correlation with angiographic ejection fraction (r = 0.90, p less than 0.0001). Peak aortic blood velocity and the ratio of midleft ventricle to aortic cross-sectional areas alone correlated less well with ejection fraction (r = 0.76 and r = 0.75, p less than 0.0001, respectively). Furthermore, peak aortic blood velocity showed a significant overlap between patients with normal and those with abnormal LV function, whereas normalized peak aortic blood velocity was a better discriminator.(ABSTRACT TRUNCATED AT 250 WORDS)

Asymptomatic form of left pulmonary artery sling.

Eight patients with left pulmonary artery sling, which were asymptomatic at the time of the last consultation, are described: 2 adults and 1 child with no history of symptoms, 3 children with mild forms of airways obstruction and 2 patients with typical severe symptoms of airways obstruction in infancy. The mean follow-up of these 8 patients was 10 years (range 4 to 23), and in 1986, all were in good health and free of respiratory symptoms. The long-term prognosis is usually good.

Doppler echocardiographic measurement of low velocity motion of the left ventricular posterior wall.

A new noninvasive method using pulsed Doppler echocardiography was developed to assess left ventricular (LV) posterior wall motion dynamics. Seventeen normal subjects and 23 patients undergoing cardiac catheterization were prospectively studied. The sample volume was placed within the LV posterior wall endocardium just apical to the mitral valve sulcus using a posteriorly angulated low parasternal view. The wall filter was set at 100 Hz to record the low velocities of the LV posterior wall motion. The Doppler signal was morphologically similar to the rate of change of the LV posterior wall endocardium excursion obtained by a digitized M-mode echocardiogram, and showed 3 major waves: a systolic wave (S), an early diastolic wave (E) and a late diastolic wave (A). The peak velocities of LV posterior wall endocardium excursion were also determined by M-mode echocardiographic technique. We found a significant linear correlation between peak E-wave velocity and M-mode peak diastolic endocardial velocity (r = 0.90, p less than 0.001) and between peak S-wave velocity and M-mode peak systolic endocardial velocity (r = 0.81, p less than 0.001). M-mode peak systolic endocardial velocity showed an important overlap between control subjects and patients with normal and patients with abnormal LV posterior wall motion on the angiogram. In contrast, peak S-wave velocity was a better discriminator, and a peak S-wave velocity less than 7.5 cm/s was associated with abnormal LV posterior wall motion with an 83% sensitivity, 100% specificity and 95% accuracy. In patients with coronary artery disease but normal systolic LV posterior wall motion and normal global systolic LV function, peak S-wave velocity was not different when compared to control subjects. Peak E-wave velocity and E/A were significantly lower than in control subjects (p less than 0.01) and peak A-wave velocity was greater (p less than 0.01). In conclusion, these data suggest that pulsed Doppler echocardiography can be used for the direct analysis of LV posterior wall instantaneous low velocities and appears to be more informative than M-mode technique for systolic measurements. Thus, detection of abnormal LV posterior wall diastolic motion by pulsed Doppler echocardiography may, upon additional confirmation, be used as a new noninvasive method to gain insight into global LV diastolic performance.

Assessment of right ventricular outflow tract in children by two-dimensional echocardiography using a new subcostal view. Angiocardiographic and morphologic correlative study.

Evaluation of the right ventricular (RV) outflow tract in congenital heart disease is extremely important for surgical management. Therefore, the value of 2-dimensional echocardiography (2-D echo) to assess the RV outflow tract was studied using a new approach: the subcostal elongated right oblique view. Twenty normal children and 49 children with congenital heart disease, aged 1 day to 11 years, were studied. Significant pulmonary infundibular obstruction was present in 22 patients with conotruncal malformations. To obtain the subcostal elongated right oblique view from the short-axis view at the aortic valve level, the transducer was slightly rotated clockwise with an anterior angulation of about 30 degrees so that the ascending aorta was seen in its long axis, providing an image similar to that obtained by a right ventriculogram in the elongated right anterior oblique view. The deviation of infundibular septum was appreciated by measurement of the angle alpha, defined by the long axis of the infundibular septum and the plane of aortic cusps. This view could be obtained in 64 patients (92%). In correlation with angiographic or anatomic data, the subcostal elongated right oblique view permitted recognition of several types of RV outflow tract: type I--normally formed RV outflow tract; type II--disorganized RV outflow tract with obstruction (alpha less than 90 degrees); type III and IV--disorganized RV outflow tract with obstruction (alpha greater than 90 degrees). This view could visualize the crista supraventricularis in type I, but also the anatomic components of RV outflow tract that may contribute to obstruction in the other types: infundibular septum, septoparietal trabeculations and trabecula septomarginalis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of diltiazem on myocardial infarct size estimated by enzyme release, serial thallium-201 single-photon emission computed tomography and radionuclide angiography.

Diltiazem is a calcium antagonist with demonstrated experimental cardioprotective effects. Its effects on myocardial infarct size were studied in 34 patients admitted within 6 hours after the first symptoms of acute myocardial infarction. These patients were randomized, double-blind to placebo or diltiazem (10-mg intravenous bolus followed by 15 mg/hr intravenous infusion during 72 hours, followed by 4 X 60 mg during 21 days). Myocardial infarct size was assessed by plasma creatine kinase and creatine kinase-MB indexes, perfusion defect scores using single-photon emission computed tomography with thallium-201 and left ventricular ejection fraction measured by radionuclide angiography. Tomographic and angiographic scanning was performed serially before randomization, after 48 hours and 21 days later. Groups were comparable in terms of age, sex, inclusion time and baseline infarct location and size. Results showed no difference in creatine kinase and creatine kinase-MB data between controls and treated patients, a significant decrease in the perfusion defect scores in the diltiazem group (+0.1 +/- 3.0 placebo vs -2.2 +/- 1.9 diltiazem, p less than 0.02) and a better ejection fraction recovery in the diltiazem group (-4.2 +/- 7.4 placebo vs +7.7 +/- 11.2 diltiazem, p less than 0.05). Myocardial infarct size estimates from perfusion defect scores and enzyme data were closely correlated. These preliminary results suggest that diltiazem may reduce ischemic injury in acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Right ventricular overload and induced sustained ventricular tachycardia in operatively "repaired" tetralogy of Fallot.

The aim of the study was to evaluate the main predictors of the inducibility of sustained ventricular tachycardia (VT) in patients with repaired tetralogy of Fallot. Thirty-five patients (age 12 +/- 6 years) underwent right-sided cardiac catheterization, echocardiography, radionuclide angiography and ventricular stimulation; 10 had (group 1) and 25 had no (group 2) sustained VT. Group 1 patients were significantly older at the time of surgery and had longer follow-up periods (7 +/- 3 vs 4 +/- 4 years, p less than 0.02; and 12 +/- 4 vs 5 +/- 2 years, p less than 0.001, respectively). Right ventricular (RV) systolic pressure, end-systolic and end-diastolic normalized RV volumes were higher in group 1 (48 +/- 14 vs 38 +/- 11 mm Hg, p less than 0.05; 1.23 +/- 0.2 vs 0.86 +/- 0.17, p less than 0.001; and 2.35 +/- 0.37 vs 1.70 +/- 0.22, p less than 0.001, respectively). RV end-diastolic pressure, left ventricular and RV ejection fractions were similar in the 2 groups. A stepwise discriminant analysis was made to predict patients with inducible sustained VT (group 1): Time period from surgery to follow-up (p less than 0.001), normalized RV end-systolic volume (p less than 0.002) and RV systolic pressure (p = 0.01) were higher in group 1 and allowed classification of 90% of patients in group 1 and 96% in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of previous angina pectoris and collateral flow to preserve left ventricular function in the presence or absence of myocardial infarction in isolated total occlusion of the left anterior descending coronary artery.

The aim of this study was to determine whether previous angina pectoris and collateral circulation influenced myocardial function after isolated coronary occlusion. In 58 consecutive patients, coronary angiography showed a complete isolated occlusion of the left anterior descending coronary artery; 43 patients (74%) had previous myocardial infarction. Duration of previous angina pectoris was defined as the time from the first ischemic symptom to the date of myocardial infarction or of coronary angiography in the absence of myocardial infarction. Left ventricular ejection fraction was measured on the 30 degrees right anterior oblique projection of the left ventricular angiogram. Collateral circulation was graded as follows: none or filling limited to side branches (group 1) and partial or complete filling of the epicardial arterial segment (group 2). Group 2 (40 patients) had higher ejection fraction (57 vs 38%; p less than 0.0001) and longer duration of previous angina pectoris (11 vs 0.1 months; p less than 0.002) than group 1 (18 patients). A longer duration of previous angina pectoris probably allows collateral development before coronary occlusion in 1-vessel coronary artery disease, thereby limiting myocardial damage.

Value of esophageal pacing in evaluation of supraventricular tachycardia.

Esophageal stimulation was performed in 40 patients who had spontaneous paroxysmal supraventricular tachycardias (SVTs). The purpose of this study was to look for the most sensitive stimulation protocol and criteria that would help to define the mechanism of reentry. In 20 patients (group I) atrial pacing up to second-degree atrioventricular block was performed under control conditions and isoproterenol, and SVT was induced in 14 patients (70%), 11 in the control state and 3 while receiving isoproterenol. In 20 patients (group II) atrial pacing and programmed atrial stimulation using 1 and 2 extrastimuli delivered at 2 cycle lengths (600 and 500 ms) was performed in the control state and while receiving isoproterenol. SVT was induced in all patients, in 13 patients in the control state and in 7 while receiving isoproterenol. Programmed stimulation always induced SVT and was the only method capable of tachycardia induction in 14 patients. The mechanism of SVT could be established in 91%. The measurement of the ventriculoatrial interval was the most useful sign to define the site of reentry. Occurrence of a bundle branch block helped to delineate the mechanism in 4 patients. When a positive P wave in V1 preceded the esophageal atrial electrocardiogram, it suggested that there was reentry through a left-sided accessory atrioventricular connection in 6 patients. SVT could always be induced by programmed atrial stimulation in the control state and under isoproterenol. The location of the P wave in V1 compared to the ventriculogram and the esophageal electrocardiogram helped to define the mechanism of tachycardia.

Association of del(11)(p15.1p12), aniridia, catalase deficiency, and cardiomyopathy.

We report another patient with del(11p) and aniridia, catalase deficiency, and cardiomyopathy. This association is confirmed from a review of previously reported cases. Since other dysplasias are known in this syndrome, the hypertrophic cardiomyopathy in del(11p) children may also represent an abnormality of tissue development.

Clarithromycin in the treatment of Mycobacterium avium lung infections in patients without AIDS. Clarithromycin Study Group of France.

Mycobacterium avium complex infections, common in patients with AIDS as either pulmonary or disseminated disease, are infrequent in patients without AIDS. Participants were 45 HIV-negative patients with lung disease and positive sputum cultures for M avium; 10 had documented immunocompromise, and 24 had preexisting lung disease. Clarithromycin dosage was 500 to 2,000 mg daily (mean +/- SD = 1,633 +/- 432 mg). The drug was administered either alone (n = 14) or in combination with rifampin (n = 8), aminoglycoside (n = 1), quinolone (n = 10), clofazimine (n = 18), isoniazid (n = 5), ethambutol (n = 9), pyrazinamide (n = 1), or minocycline (n = 6). At 3 months, 36 patients among 39 bacteriologically assessed had negative sputum cultures, 3 had positive culture, 3 were dead, and 3 discontinued treatment. At the end of treatment, 32 patients remained negative, 7 were positive. The success rate was 15 of 22 (64%) in patients previously treated with antimycobacterial drugs for M avium disease and 17 of 23 (74%) in new patients. Adverse effects included mild hearing loss (n = 4), increase in liver enzyme levels (n = 5), and gastrointestinal pain (n = 10, two of whom had to stop treatment). Patients stopped treatment after 300 +/- 186 days due to side effects (3), death (4), or the patient's (5) or physician's decision (33). During the follow-up, one patient suffered a relapse with peripheral lymph nodes. A daily dose of 30 mg/kg of clarithromycin in the treatment of M avium infections appears to be effective and safe. Concomitant drug therapy should be assessed for its ability to prevent relapse.

Mycobacterial lung disease in cystic fibrosis: a prospective study.

BACKGROUND: Patients with cystic fibrosis (CF) may be predisposed to airway infections with unusual organisms, such as mycobacteria. The aim of the study was to determine the incidence and clinical picture of mycobacterial infection in CF children. METHODS: At least 2 acid-fast bacillus (AFB) smears and mycobacterial cultures were performed on a prospective basis on 682 sputum specimens from 106 patients during a 1-year period. RESULTS: Thirty-three percent of the cultures were contaminated with other bacteria. Seven children had at least one sputum culture positive for one mycobacterium. Five children had only one positive AFB culture. Their clinical status and lung function remained stable during follow-up. Two teenagers with severe lung disease had several positive AFB smears and cultures for Mycobacterium chelonae and Mycobacterium abscessus. The isolation of M. chelonae and M. abscessus was associated with a clinical and functional decline. Clarithromycin treatment resulted in temporary improvement with the disappearance of the mycobacteria after 6 months of treatment. This prospective study shows an incidence of 2.3% for positive cultures. The prevalence was 6.6% for mycobacterial colonization but only 1.9% for mycobacterial lung disease in our pediatric population. CONCLUSIONS: We recommend performing AFB smears and cultures in CF children with severe lung disease and/or during a lung exacerbation. In these patients persistence of M. chelonae or M. abscessus in sputum should lead to consideration of treatment with clarithromycin.

Iron and Mycobacterium tuberculosis infection.

BACKGROUND: iron is known to play a role in the susceptibility to and outcome of several infections. In view of the increasing worldwide problem of tuberculosis, it may be important to ascertain whether this is also the case with this infection. OBJECTIVES: (1) to review studies conducted in vitro, in experimental animals, and in humans that provide evidence that iron status may influence the occurrence and outcome of tuberculosis. (2) To perform an in vivo study in mice, examining the effect of iron loading on experimental infection caused by a virulent strain of Mycobacterium tuberculosis. RESULTS: we studied the effect of iron loading on the growth in spleen and lungs of a virulent strain of M. tuberculosis, injected i.v. in female Balb/C mice. At sacrifice on day 42 after the experimental infection, the iron-loaded mice presented a significantly enhanced multiplication of M. tuberculosis in both the spleen and the lungs, when compared to the mice without iron loading. CONCLUSION: Most of the studies, including our experimental study in mice, tend to suggest that an excess of iron may enhance the growth of M. tuberculosis and worsen the outcome of human tuberculosis.

Mycobacterium avium complex common-source or cross-infection in AIDS patients attending the same day-care facility.

To delineate the epidemiology of Mycobacterium avium complex (MAC) infection in acquired immunodeficiency syndrome patients, we studied 32 case patients with disseminated MAC infection who attended the same daycare facility during a period of 13 months. Pulsed-field gel electrophoresis analysis showed very low similarity between MAC strains, suggesting that, despite close contacts between the patients, nosocomial cross-transmission or exposure to a common source of MAC did not occur.

Rapid, simple, and culture-independent detection of rpsL codon 43 mutations that are highly predictive of streptomycin resistance in Mycobacterium tuberculosis.

The substitution of codon 43 in the gene rpsL is the single most common mutation found in streptomycin-resistant Mycobacterium tuberculosis. The characterization of this mutation has been hampered by the need for prior cultivation of the mycobacteria, the need for DNA sequencing, or both. In this report we describe a simple and culture-independent technique to detect this mutation directly from sputum samples, requiring little more than a polymerase chain reaction (PCR) machine and a simple agarose minigel. There is no need for labeled probes or DNA sequencing. In a preliminary test of feasibility, interpretable results were obtained from all of 16 smear-positive and 1 of 4 smear-negative, culture-positive samples. Two of two samples containing M. tuberculosis with rpsL codon 43 mutations were correctly identified.

Angiocardiography in congenital subvalvular aortic stenosis: prognosis and operative indications.

Twenty-three patients with congenital subvalvular aortic stenosis are reviewed. The importance of classifying this stenosis into four types based on angiocardiographic findings is stressed, as are the indications for left heart catheterization during the preoperative and postoperative course of the disease. The type of congenital subvalvular aortic stenosis should be an important consideration during the discussion of operative indications in both asymptomatic and symptomatic patients.