[Computed tomography-based virtual colonoscopy: an examination useful for the choice of the surgical management of colorectal endometriosis]. / Coloscanner à l'air avec coloscopie virtuelle: arguments dans le choix du traitement chirurgical des endométrioses colorectales.

OBJECTIVE: To evaluate the use of computed tomography-based virtual colonoscopy in the preoperative assessment of colorectal endometriosis. PATIENTS AND METHODS: We included in the study consecutive women undergoing surgical management of deep infiltrating endometriosis from August 2009 to April 2010, whose colorectal involvement had been assessed by magnetic resonance imaging (MRI) and rectal endoscopic sonography (RES). Prior to surgical procedure, a computed tomography-based virtual coloscopy was performed. Computed tomography was performed by insufflating air into the distal rectum, along with an intravenous injection of contrast agent. Then, 3D reconstruction of pictures was carried out, to allow visualization of the lumen of the rectum and the colon. Data provided by virtual colonoscopy were compared to those given by other imaging techniques and surgical exploration. RESULTS: Twenty-seven patients were included in the study: 7 women underwent colorectal segmental resection, 2 full thickness excision, 15 shaving, while in 3 of them no digestive surgical step was performed. Virtual colonoscopy provided the measurement of the length and the diameter of colorectal stenosis due to infiltrating nodule through rectal and sigmoid wall, which was presenting as an endoluminal indentation. The number of patients presenting with endometriotic nodules arising on the rectum, sigmoid colon, or both of them, were respectively 13, 7 and 7. Ovarian endometriomas were responsible for extrinsic compression leading to digestive tract stenosis in nine cases. The number of lesions and their height reported to the anus were accurately assessed in 24 women out of 27 (sensitivity of 88%). The origin of the digestive tract stenosis, i.e. either infiltrating endometriotic nodules or extrinsic compression due to ovarian endometriomas, was accurately assessed in all cases, by combining information provided by virtual colonoscopy, IRM, RES and transvaginal ultrasonography. CONCLUSION: Computed tomography-based virtual colonoscopy provides useful information about the degree and the height of digestive tract stenosis due to colorectal endometriosis. In our opinion, this information is of major interest to argue the choice of shaving or full thickness excision of nodules in a majority of women presenting with colorectal endometriosis.

[Ghosal haematodiaphyseal dysplasia: a new case]. / Un nouveau cas de dysplasie hématodiaphysaire de Ghosal.

Ghosal-type hematodiaphyseal dysplasia has been first described in 1986, as a steroid-dependent anemia with endosteal broadening of the long bone's diaphyses and metaphaphyses, which makes a distinction with the periosteal reaction in Camuratti-Engelmann's disease and with Caffey's disease. Extreme pallor is first noticed and leads to search for palpable thick long bones that are not always clinically obvious. The transmission of this rare entity seems to be autosomal recessive, with a common racial background from the Middle East and the Indian subcontinent. Anemia is considerably improved by steroids, which allow to avoid blood cells transfusions, but a minimum maintenance dose is necessary to keep the hemoglobin at a normal level probably during the whole life, involving iatrogen complications. The mechanism of anemia and the genetic cause of the disease are yet unknown.

Tissue Doppler echocardiography in patients with long QT syndrome.

BACKGROUND: Congenital long QT syndrome (LQTS) is a well-defined clinical entity associated with a high mortality among untreated patients. Tissue Doppler (TD) echocardiography that has been recently introduced, facilitates wall motion analysis. Therefore, to further characterize myocardial velocity abnormalities associated with LQTS, using TD and conventional echocardiography, we compared control subjects and LQTS patients. METHODS AND RESULTS: Ten patients with mild LQTS and 14 control subjects were examined with standard and TD echocardiography. We studied myocardial velocities in basal and mid-segments of the septal, lateral, inferior and anterior walls. Peak velocity and time intervals were measured in each segment. We confirmed previously described M-mode abnormalities, demonstrated by an increase of the wall thickening time index. TD analysis demonstrated increased systolic and diastolic peak velocities for all segments in LQTS patients. Regional isovolumic relaxation time and systolic velocity half time (VHT) were significantly longer in LQTS group associated with a prolonged late systolic phase, resulting in a plateau morphology. CONCLUSION: We demonstrated that TD allows the characterization of myocardial velocity abnormalities in LQTS patients. TD measurements could become part of the routine clinical evaluation for patients potentially affected by the LQTS as a new phenotypic marker.

A reverse transcription-PCR assay to detect viable Mycoplasma synoviae in poultry environmental samples.

In order to study horizontal transmission of Mycoplasma synoviae an avian pathogen, a reverse transcription-polymerase chain reaction (RT-PCR) assay was developed to detect viable Mycoplasma in environment. The test was based on the RT-PCR of the 16S ribosomal RNA (rRNA) of Mycoplasma genus. Results showed that Mycoplasma 16S rRNA was stable up to 23 h after cell death. Therefore, the test allowed detection of viable or very recently (less than 23 h) dead mycoplasmas. M. synoviae survival in artificially contaminated water, food and soil and in the environment of M. synoviae experimentally infected turkeys was estimated by culture and RT-PCR. The RT-PCR method was then applied in a naturally infected laying hen farm showing problems of recurrent mycoplasmosis in the hens. Results confirmed the usefulness of RT-PCR in checking the efficiency of biosecurity measures and in improving cleaning and disinfection protocols.

Role of anxiety and depression in the onset of spontaneous preterm labor.

The aim of this cohort study conducted in France in 1997-1998 was to investigate the effects of antenatal anxiety and depression on spontaneous preterm labor. A consecutive series of 634 pregnant women with singleton pregnancies was included. Anxiety and depression were assessed using self-administered questionnaires: Spielberger's State-Trait Anxiety Inventory and the Edinburgh depression scale. Depression scores were dichotomized with a cutoff value suggestive of major depression. The 75th percentile was used for anxiety scores. A logistic regression analysis, controlling for sociodemographic and biomedical factors and including interaction terms, revealed that depression was positively associated with the outcome among underweight women, defined as women with a prepregnancy body mass index below 19 (adjusted odds ratio (OR) = 6.9, 95% confidence interval (CI): 1.8, 26.2). A similar result was observed for trait anxiety in women with a history of preterm labor (adjusted OR = 4.8, 95% CI: 1.1, 20.4). The association was close to significance for state anxiety in women with vaginal bleeding (adjusted OR = 3.6, 95% CI: 0.9, 14.7). These findings show that anxiety and depression, when combined with specific biomedical factors, are associated with spontaneous preterm labor. A synergic action of psychological and biomedical factors on the secretion of placental corticotropin-releasing factor is hypothesized.

Ross operation for active culture-positive aortic valve endocarditis with extensive paravalvular involvement.

BACKGROUND: We evaluated the midterm results of the Ross operation in active advanced endocarditis. METHODS: Between June 1994 and June 2000 a pulmonary autograft aortic root replacement was performed in 11 consecutive patients who had urgent or emergent procedures for active endocarditis with extensive involvement of the aortic root (10 native, 1 prosthetic). Patients ranged in age from 26 to 45 years (median, 33 years). Indications for operation were uncontrolled infection (n = 5), hemodynamic deterioration (n = 3), or both (n = 3). Four patients were in the New York Heart Association class III, 6 in class IV, and 1 was operated on while in cardiogenic shock. Four patients (36%) suffered an embolic cerebrovascular accident preoperatively. The endocarditis affected the mitral valve in 2 patients and the tricuspid valve in 1 patient. RESULTS: There was no early or late death. Recurrent endocarditis was not detected in any of the patients during the follow-up period ranging up to 72 months (median, 40 months). CONCLUSIONS: The autograft may well be the best substitute for aortic root reconstruction in advanced endocarditis.

Effect of mitral valve surgery on exercise capacity, ventricular ejection fraction and neurohormonal activation in patients with severe mitral regurgitation.

OBJECTIVES: The purpose of this study was to prospectively investigate the effects of surgical correction of mitral regurgitation (MR) on exercise performance, cardiac function and neurohormonal activation. BACKGROUND: Little is known about the effect of surgical correction of MR on functional status or on neurohormonal activation. METHODS: Cardiopulmonary exercise test, radionuclide angiography and blood samples for assessment of neurohormonal status were obtained in 40 patients with nonischemic MR before and within one year (216+/-80 days) after surgery. Twenty-four patients underwent mitral valve repair (MVr), and 16 underwent valve replacement (VR) with anterior chordal transection. RESULTS: Despite an improvement in New York Heart Association functional class, exercise performance did not change (peak oxygen consumption: 19.3+/-6.1 to 18.5+/-5.6 ml/kg/min, percentage of maximal predicted oxygen consumption: 79.5+/-18.2% to 76.8+/-16.9%). After surgery, left ventricular (LV) ejection fraction (EF) decreased (64.2+/-10.3% to 59.9+/-11.4%, p = 0.003) while right ventricular (RV) EF increased (41.4+/-9.6% to 44.7+/-9.5%, p = 0.03). Left ventricular EF did not change after MVr (64.3+/-11.5% to 61.5+/-12.2%), but RVEF improved (40.4+/-9.2% to 46.0+/-10.0%, p = 0.02). In contrast, VR was associated with an impairment of LV function in the apicolateral area and a decrease in LVEF (64.1+/-8.5% to 57.4+/-10.0%, p = 0.01), whereas RVEF did not change (42.9+/-10.3% to 42.8+/-8.6%). Moreover, there was only a slight decrease in neurohormonal activation after surgery. CONCLUSIONS: Despite an improvement in symptomatic status, exercise performance was not improved seven months after either MVr or VR for MR, and neurohormonal activation persisted. Compared with MVr, VR resulted in a significant impairment of cardiac function in this study.

A PCR assay used to study aerosol transmission of Actinobacillus pleuropneumoniae from samples of live pigs under experimental conditions.

The study describes a polymerase chain reaction (PCR) assay for the detection of Actinobacillus pleuropneumoniae. The test is based on the amplification of the omlA gene coding for an outer membrane protein of A. pleuropneumoniae. To test the specificity of the reaction, 19 other bacterial species related to A. pleuropneumoniae or isolated from pigs were assayed. They were all found negative in the PCR assay. The detection threshold of the test was 10(2) A. pleuropneumoniae CFU/assay. The test was then applied to the detection of A. pleuropneumoniae from tonsillar biopsies and tracheobronchial lavage fluids of pigs without a culture step. The detection of A. pleuropneumoniae in these samples was performed by PCR, by conventional culture and by bacteriology with immunomagnetic beads. The number of samples that were found positive by PCR was almost three times higher than the number of samples from which A. pleuropneumoniae was isolated by both bacteriological techniques. The detection of A. pleuropneumoniae in these samples allowed us to demonstrate its aerosol transmission to pigs under experimental conditions. The trial involved 18 specific pathogen free pigs. Six pigs, infected with A. pleuropneumoniae, were located in a unit A, together with four non-infected animals (contact pigs). Eight non-infected pigs (reporter pigs) were located in a unit B, adjacent to A. We detected A. pleuropneumoniae in samples from infected animals but also from 'contact' (unit A) and 'reporter' (unit B) pigs. The results of this study show that the simple preparation of the samples followed by the PCR assay may be a useful tool for epidemiological studies.

Echocardiographic follow-up after Ross procedure in 100 patients.

The Ross procedure could provide an ideal aortic valve replacement method in children and young adults. We evaluated midterm echocardiographic results to assess pulmonary homograft function as well as pulmonary autograft dimensions and function. In all, 105 patients (26 women and 79 men) underwent the Ross procedure; median age at implant was 29 years. All patients underwent free root replacement. Transvalvular gradients and autograft dimensions were measured at 3 levels (annulus, sinuses of Valsalva, and proximal aorta) at discharge, at 6 months, and annually thereafter. Perioperative mortality was 4.7%. The mean period for echocardiographic follow-up in 100 patients was 32.7 months (range 0.5 to 7 years), during which 4 noncardiac-related deaths occurred. Two patients underwent late reintervention. No moderate or severe regurgitation was recorded. There was 1 case of mild homograft regurgitation and 4 of mild autograft regurgitation at late follow-up. Autograft peak gradients were low and reproducible (5 +/- 2.8 mm Hg at discharge vs 5.5 +/- 3.5 mm Hg at last follow-up, p = NS). Homograft peak gradients increased significantly without severe obstruction (7.8 +/- 5.7 mm Hg at discharge vs 15.8 +/- 9.2 mm Hg at last follow-up). The diameter of the autograft annulus was stable during follow-up, whereas autograft dimensions at sinuses and proximal aorta increased significantly. One group of patients was identified with sinus diameter increases >20% (group A). The 90 remaining patients were classified into group B. The only parameter significantly different between the 2 groups was the sinus diameters measured at discharge (1.74 cm/m2 (group A) vs 1.92 cm/m2 (group B); p = 0.036). In 100 patients and with echocardiographic follow-up for up to 7 years, the Ross procedure showed excellent results. For 10% of patients, we observed a 20% dilation of sinus diameters, but in only 3 patients (3%) was this beyond the upper normal limit.

Experimental aerosol transmission of Actinobacillus pleuropneumoniae to pigs.

In order to demonstrate the possible role of aerosol in the transmission of Actinobacillus pleuropneumoniae, an experiment including 18 specific pathogen-free (SPF), 10-week-old piglets, randomly distributed into 2 adjacent units, was carried out. In these facilities, air was forced through absolute filters to prevent any contact with infectious agents. During the first 6 d post inoculation, the 2 units were connected by a rectangular opening and the air circulation was forced by the ventilation system from unit A (inoculated pigs) to unit B (non-inoculated pigs). The A. pleuropneumoniae strain (biovar 1 serovar 9) was isolated in France from an outbreak of porcine pleuropneumonia. Two different infecting doses, 10(7) cfu/animal and 10(8) cfu/animal, were inoculated by intranasal route in 6 pigs of unit A. The infection spread quickly from the inoculated pigs to the non-inoculated pigs. Clinical signs were acute during the 4 d post inoculation: hyperthermia, respiratory distress and, sometimes, death (6 pigs of the unit A and 2 pigs of the unit B). All pigs seroconverted against A. pleuropneumoniae serovar 9 within 2 weeks. Lung lesions were severe: fibrinous pleurisy and lung hemorrhages in the acute stage, pleural adherences and focal pulmonary necrosis in the chronic stage. Actinobacillus pleuropneumoniae was isolated from the tonsils and/or lungs in 16 animals. It could be also isolated from the air of the experimental unit. This study showed that A. pleuropneumoniae was readily transmitted through aerosol over a distance of at least 2.5 m.

Mid-term comparative follow-up after aortic valve replacement with Carpentier-Edwards and Pericarbon pericardial prostheses.

BACKGROUND: The first generation of pericardial valves had a high rate of premature deterioration. The aim of this study was to compare the outcome after aortic valve replacement with second generation pericardial prostheses (Pericarbon and Carpentier-Edwards). METHODS AND RESULTS: Between 1987 and 1994, 162 patients underwent aortic valve replacement with either a Pericarbon (n=81, 69+/-11 years) or a Carpentier-Edwards (n=81, 70+/-11 years) pericardial prosthesis. Mean follow-up was 4.4+/-2.7 years for Pericarbon and 4.8+/-2.4 years for Carpentier-Edwards valves (P=0. 27), giving a total follow-up of 745 patient-years. Thirty-day mortality and 5-year actuarial survival were, respectively, 6.2% and 63.2+/-5.7% in the Pericarbon group and 6.2% and 63.5+/-5.6% in the Carpentier-Edwards group. At 8 years, freedom from (and linearized rates per patient-year) thromboembolism, structural failure, and all valve-related events were, respectively, 91.8+/-3.6% (1.4%), 76. 9+/-8.7% (2.5%), and 58.4+/-9.3% (5.6%) in the Pericarbon group and 94.4+/-2.7% (1%), 100% (0%, P<0.01), and 88.8+/-3.7% (2%, P<0.05) in the Carpentier-Edwards group. There were 9 (11.1%) Pericarbon structural failures related predominantly to severe calcification and stenosis. The actual reoperation rate was 7.4% (1.6% per patient-year) in the Pericarbon group for fibrocalcific degeneration (n=3), periprosthetic leak (n=1), endocarditis (n=1), and aortic dissection (n=1). There was neither structural valve failure nor valve reoperation in the Carpentier-Edwards group. Echocardiographic review of 70 patients from 85 survivors (82.3%) found 4 additional Pericarbon valves with signs of early structural failure but no Carpentier-Edwards valve with such changes. CONCLUSIONS: Eight years after aortic valve replacement, Pericarbon pericardial prostheses compared unfavorably with Carpentier-Edwards pericardial prostheses, with a high incidence of structural valve failure and reoperation.

[Effect of resection of the anterior chordae on cardiac function after surgical correction of mitral valve insufficiency]. / Effet de la résection des cordages antérieurs sur la fonction cardiaque après correction chirurgicale d'une insuffisance mitrale.

The preservation of cardiac function in surgical correction of mitral regurgitation implies partially or totally preserving the subvalvular apparatus. However, the conservation of the whole subvalvular apparatus during mitral valve replacement is technically difficult as the anatomical conditions are not always favourable. In order to determine the consequences of isolated resection of the anterior chordae, the authors studied global and segmental cardiac function by isotopic angiocardiography after mitral valve repair (n = 23) or replacement with conservation of the posterior chordae (n = 16) in 39 patients with isolated, non-ischaemic mitral regurgitation. The left ventricular ejection fraction decreased after valve replacement (64.1 +/- 8.5% to 57.4 +/- 10%, p = 0.01) but not after mitral valve repair (65 +/- 11.3% to 62.1 +/- 12.2%, p = NS). The ejection fractions of segments 4 and 5, corresponding to the zones of insertion of the anterior papillary muscle, decreased after valve replacement compared with repair (segment 4: -9 +/- 13.7 versus +2 +/- 11.3, p = 0.01) (segment 5: -15 +/- 13.2 versus 2 +/- 11.7, p = 0.003). The right ventricular ejection fraction improved after valve repair (40.9 +/- 9.1% to 46.4 +/- 10.1%, p = 0.03), whereas it remained unchanged after valve replacement (42.9 +/- 10.3% to 42.8 +/- 8.6%, p = NS). These results indicate a deleterious effect of isolated resection of the anterior chordae on cardiac function during mitral valve replacement with localised abnormalities of left ventricular function. This study supports the rationale of mitral valve repair or conservation of the anterior and posterior chordae during valve replacement for isolated mitral regurgitation.

Radioprotection of DNA by spermine: a molecular modelling approach.

PURPOSE: To observe and explain the sequence-dependence of DNA radioprotection by spermine. MATERIALS AND METHODS: Sequencing gel electrophoresis was used to analyse the probability of frank strand break (FSB) induction at each nucleotide site. Molecular modelling of complexes of DNA with spermine molecules and of a curved electrically null DNA has been performed. RESULTS: The effect of spermine on radiation-induced strand breakage varied significantly along the studied fragment. At low spermine concentration, some sequences were protected while others were unprotected. Molecular modelling calculations show that the most electro-negative sites are located in the minor or in the major groove of DNA. The positively charged spermine (Z=+4) should preferentially bind to such sites. When bound in the minor groove, spermine triggers a reduction of the accessibility of radiolytic attack sites to OH* radicals. This is due to induced structural modifications and to the masking of attack sites. In the case of major groove binding, no reduction of accessibility occurs. This type of binding can explain the lack of protection of sequences with electro-negative sites in the major groove. At high spermine concentration, the fragment is strongly protected. A nucleosome-like pattern of breakage with periodically distributed regions of protection was observed. Molecular modelling calculations show that the accessibility of the attack sites in a curved electrically null DNA is also periodically reduced. CONCLUSIONS: Molecular modelling of DNA-spermine complexes that takes into account the electrostatic properties of DNA, allows an explanation of the experimentally observed effects of spermine on DNA radiosensitivity.

No association between dopamine D1, D2, and D3 receptor genes and manic-depressive illness.

BACKGROUND: The dopaminergic receptor genes are candidate genes for manic-depressive illness (MDI). To test this putative involvement we used a case-control study on samples from the native population of the northwest part of France. METHODS: Fifty patients for D1 and D2, 61 patients for D3, and 86-223 controls were tested. RESULTS: No significant association was found between allelic frequencies or genotype counts and MDI, even when the data were pooled with those from published studies. CONCLUSIONS: Single mutations of either of the studied receptor genes are not major determinants of MDI.

Aortic root replacement with a pulmonary autograft in young adults: medium-term results in 70 patients.

BACKGROUND: Pulmonary autograft aortic valve replacement has been introduced in our institution in selected adult patients in light of the known disadvantages and limitations of conventional prosthetic valves. METHODS: We prospectively evaluated the use of the pulmonary autograft in a series of 70 young adults (31.2+/-8.7 years, range 16 to 49 years) operated on from March 1992 to April 1997 with aortic root replacement only. RESULTS: There were no in-hospital deaths and two noncardiac-related late deaths during follow-up of up to 62 months (mean 33 months). Thromboembolic complications were not observed. One patient required reoperation for infective endocarditis 4.3 years after surgery. Discharge echo-Doppler studies showed normal autograft and allograft valve function. Serial echo-Doppler studies showed no significant progression of aortic insufficiency and no dilatation of the autograft. A severe stenosis of the pulmonary allograft developed in 1 patient. CONCLUSION: Aortic root replacement with a pulmonary autograft, although more complex than conventional prosthetic valve replacement, is a safe, effective, and reproducible procedure in properly selected adult patients. Long-term results remain to be evaluated.

Sequence-dependent variations of DNA structure modulate radiation-induced strand breakage.

Using a 80 base pair DNA fragment, the sequence-dependence was compared for: (i) the probability of fast neutrons induced strand breakage, (ii) the accessibility of the H4'- and H5'-atoms to OH. attack, (iii) the width of the minor groove, and (iv) the probability of OH. reactions with H4'- or H5'-atoms. The probability of strand breakage was measured using sequencing gel electrophoresis. The accessibility and the probability of reaction were calculated for the energy-minimized modelled DNA fragment. A Monte-Carlo simulation was used for calculating the probabilities of H-atom abstraction by OH.. It was observed that reduced breakage occurs in sequences exhibiting low accessibility of H4' and H5'2 and low probability of H-atom abstraction by OH., due to a narrow, minor groove. This shows that the breakage probability at a given nucleotide site is not determined by the chemical nature of the nucleotide (A, T, G or C), but mainly by the local sequence-modulated intrinsic structure. Fitting the experimental results with the calculated probabilities of reaction suggests that a C4'-centered radical evolves towards a strand break three times more efficiently than the C5' one, and that half of the breaks occur via the 4'-path and half via the 5'-path.

Systemic infection related to endocarditis on pacemaker leads: clinical presentation and management.

BACKGROUND: Endocarditis related to pacemaker (PM)-lead infection is a rare but serious complication of permanent transvenous pacing. To determine in which situations the diagnosis should be evoked and to determine optimal management, we reviewed our experience with endocarditis related to PM-lead infection. METHODS AND RESULTS: Fifty-two patients were admitted for endocarditis related to PM-lead infection. The presentation was acute in 14 patients, with onset of symptoms in the first 6 weeks after the last procedure on the implant site, and chronic in 38 patients. Fever occurred in 86.5%. Clinical and/or radiological evidences of pulmonary involvement were observed in 38.4%. Pulmonary scintigraphy disclosed pulmonary infarcts in 31.2%. Local complications were found in 51.9%. Elevated C-reactive protein was found in 96.2%. A germ was isolated in 88.4% of patients and was a Staphylococcus in 93.5%. Transthoracic echocardiography demonstrated vegetations in only 23% of patients, whereas transesophageal echocardiography disclosed abnormal appearances on the PM lead in 94%. We systematically tried to ablate all the material. Two techniques were used: percutaneous ablation or surgical removal during extracorporeal circulation. All patients were treated with antibiotics after removal of the infected material. Two patients died before lead removal and 2 after surgical removal; the predischarge mortality was 7.6%, and the overall mortality was 26.9% after a follow-up of 20.1+/-13 months. CONCLUSIONS: The diagnosis of endocarditis related to PM-lead infection should be suspected in the presence of fever, complications, or pulmonary lesions after PM insertion. Transesophageal echocardiography should be performed to look for vegetations. Staphylococci are involved in the majority of these infections. The endocardial system must be entirely removed and appropriate antibiotic therapy pursued for 6 weeks.

Thiol WR-1065 and disulphide WR-33278, two metabolites of the drug ethyol (WR-2721), protect DNA against fast neutron-induced strand breakage.

The main metabolites of the cytoprotective drug Ethyol (Amifostine, WR-2721) are the thiol WR-1065 and the disulphide WR-33278 (formed by the oxidation of WR-1065). Both metabolites are well-known protectors against DNA damage induced by gamma-rays. Using supercoiled plasmid DNA and restriction fragments we show that they protect efficiently also in the case of fast neutrons. In anoxic conditions WR-1065 (Z = +2) protects by scavenging of OH. and by 'chemical repair' (by H donation from its SH function). WR-33278 (Z = +4) protects by scavenging of OH. and, in the case of the supercoiled plasmid DNA, by reducing the accessibility of radiolytic attack sites via the induction of packaging of DNA in liquid-crystalline condensates (observed by circular dichroism). Because of this second mechanism, the plasmid DNA is more efficiently protected by WR-33278 than by WR-1065, at concentration ratios > 1 drug/4 nucleotides. Moreover, using sequencing gel electrophoresis of irradiated fragments of known sequence, we show that the protection by the two metabolites is non-homogeneously distributed along the DNA sequence, with 'hot spots' of protection and with unprotected regions. Based on presented molecular modelling results we explain the sequence dependence of radioprotection by structural variations induced by the binding of the drugs.

Transcranial high-intensity Doppler signals in patients with mechanical heart valve prostheses: their relationship with abnormal intracavitary echoes.

BACKGROUND AND AIMS OF THE STUDY: In preceding studies, we reported that abnormal Doppler signals of high intensity (HITS) were frequently found in the cerebral arteries of patients with prosthetic mechanical heart valves. These signals should be attributed either to air microbubbles, possibly due to cavitations or to solid emboli elements. On the other hand, the presence of abnormal intracardiac echoes has been reported in patients with mechanical valves. These echoes should be also attributed to air microbubbles or to formed elements. Although in vitro experiments are in favor of the first explanation, the discussion of their origin remains open. METHODS: Among patients subjected to a transesophageal echocardiography (TEE), we selected subjects with mechanical prosthetic heart valves, according to the following criteria: (i) normally functioning valves; (ii) bright echoes suggesting microbubbles, inside the prosthetic valve and/or upstream from it (left ventricular outflow tract or left atrium); (iii) no morphological lesions that could generate solid microemboli at the prosthetic level; (iv) normal carotid arteries, as investigated by color echo-Doppler. RESULTS: Twenty patients were selected: 11 men and nine women of age range 40-64 years. They were implanted with mechanical heart valves (24 Saint-Jude Medical, three Björk-Shiley and one CarboMedics) in the mitral position (10), aortic position (two), or mitral and aortic position (eight) for periods ranging from 10 days to 17 years. There was no major left ventricular dysfunction (mean end-diastolic diameter 51.8 mm; mean ejection fraction 59%). The mean diameter of the left atrium was 46.1 mm. All but three patients were in sinus rhythm; seven had presented with a transient ischemic attack or amaurosis within the six months preceding the investigation. Immediately after TEE, Doppler signals were recorded on the middle cerebral arteries (MCA) during 10 minutes on each side, and the abnormal Doppler signals were counted. Seventeen subjects (85%) exhibited HITS repetition rate from 0.2 to 5.5 per min. CONCLUSION: The percentage of patients with HITS in a non-selected group with mechanical heart valves was about 50%, as observed in previous studies. It appears that in a selected group of patients the percentage with HITS is consistently higher. Therefore, HITS and abnormal intracardiac echoes could have a common origin.