Transcranial and pulsed focused ultrasound that activates brain can accelerate remyelination in a mouse model of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) impacts approximately 400,000 in the United States and is the leading cause of disability among young to middle aged people in the developed world. Characteristic of this disease, myelin within generally focal volumes of brain tissue wastes away under an autoimmune assault, either inexorably or through a cycle of demyelination and remyelination. This centrally located damage produces central and peripheral symptoms tied to the portion of brain within the MS lesion site. Interestingly, Gibson and colleagues noted that optical activation of transgenically tagged central neurons increased the thickness of the myelin sheath around those neurons. Since ultrasound, delivered transcranially, can also activate brain focally, we hypothesized that ultrasound stimulation that followed the temporal pattern of Gibson et al. applied to MS lesions in a mouse model might either decelerate the demyelination phase or accelerate its remyelination phase. METHODS: We created a temporal pattern of ultrasound delivery that conformed to that of Gibson et al. and capable of activating mouse brain. We then applied ultrasound, transcranially, following that temporal pattern to separate cohorts of a mouse model of multiple sclerosis, using three different ultrasound carrier frequencies (0.625 MHz, 1.09 MHz, 2.0 MHz), during each of the demyelinating and remyelinating phases. After identifying the most promising protocol and MS brain state through qualitative analysis of myelin content, we performed additional studies for that condition then assayed for change in myelin content via quantitative analysis. RESULTS: We identified one ultrasound protocol that significantly accelerated remyelination, without damage, as demonstrated with histological analysis. CONCLUSION: MRI-guided focused ultrasound systems exist that can, in principle, deliver the ultrasound protocol we successfully tested here. In addition, MRI, as the clinical gold standard, can readily identify MS lesions. Given the relatively low intensity values of our ultrasound protocol - close to FDA limits - we anticipate that future success with this approach to MS therapy as tested using more realistic MS mouse models may one day translate to clinical trials that help address this devastating disease.

Experimental pain in the groin may refer into the lower abdomen: Implications to clinical assessments.

OBJECTIVES: To investigate the effects of experimental adductor pain on the pain referral pattern, mechanical sensitivity and muscle activity during common clinical tests. DESIGN: Repeated-measures design. METHODS: In two separate sessions, 15 healthy males received a hypertonic (painful) and isotonic (control) saline injection to either the adductor longus (AL) tendon to produce experimental groin pain or into the rectus femoris (RF) tendon as a painful control. Pain intensity was recorded on a visual analogue scale (VAS) with pain distribution indicated on body maps. Pressure pain thresholds (PPT) were assessed bilaterally in the groin area. Electromyography (EMG) of relevant muscles was recorded during six provocation tests. PPT and EMG assessment were measured before, during and after experimental pain. RESULTS: Hypertonic saline induced higher VAS scores than isotonic saline (p<0.001), and a local pain distribution in 80% of participants. A proximal pain referral to the lower abdominal region in 33% (AL) and 7% (RF) of participants. Experimental pain (AL and RF) did not significantly alter PPT values or the EMG amplitude in groin or trunk muscles during provocation tests when forces were matched with baseline. CONCLUSIONS: This study demonstrates that AL tendon pain was distributed locally in the majority of participants but may refer to the lower abdomen. Experimental adductor pain did not significantly alter the mechanical sensitivity or muscle activity patterns.

Iodinated X-ray contrast agents: Photoinduced transformation and monitoring in surface water.

Conventional wastewater treatment methods have shown to be unsuitable for a complete elimination of iodinated X-ray contrast agents (ICMs), which have thus been found in wastewater treatment plant (WWTP) effluent and in surface water. Once in the surface water, they could be transformed through different processes and form several transformation products that may need to be monitored as well. To this end, we studied the abatement and transformation of ICMs by combining laboratory experiments with in field analyses. We irradiated different aqueous solutions of the selected pollutants in the presence of TiO2 as photocatalyst, aimed to promote ICMs degradation and to generate photoinduced transformation products (TPs) similar to those occurring in the environment and effluent wastewater. This experimental strategy has been applied to the study of three ICMs, namely iopromide, iopamidol and diatrizoate. A total of twenty-four, ten, and ten TPs were detected from iopamidol, diatrizoate and iopromide, respectively. The analyses were performed using a liquid chromatography-LTQ-FT-Orbitrap mass spectrometer. The mineralization process and acute toxicity evolution were assessed as well over time and revealed a lack of mineralization for all ICMs and the formation of harmful byproducts. After characterizing these transformation products, WWTP effluent and surface water taken from several branches of the Chicago River were analyzed for ICMs and their TPs. HRMS with MS/MS fragmentation was used as a confirmatory step for proper identification of compounds in water and wastewater samples. All three of ICM were detected in the effluent and surface water samples, while no significant amount of TPs were detected.

Resisted adduction in hip neutral is a superior provocation test to assess adductor longus pain: An experimental pain study.

The criterion of long-standing groin pain diagnoses in athletes usually relies on palpation and clinical tests. An experimental pain model was developed to examine the clinical tests under standardized conditions. Pain was induced by hypertonic saline injected into the proximal adductor longus (AL) tendon or rectus femoris (RF) tendon in 15 healthy male participants. Isotonic saline was injected contralaterally as a control. Pain intensity was assessed on a visual analog scale (VAS). Resisted hip adduction at three different angles and trunk flexion were completed before, during, and after injections. Pain provocation in the presence of experimental pain was recorded as a true positive compared with pain provocation in the non-pain conditions. Similar peak VAS scores were found after hypertonic saline injections into the AL and RF and both induced higher VAS scores than isotonic saline (P < 0.01). Adduction at 0° had the greatest positive likelihood ratio (+LR = 2.8, 95%CI: 1.09-7.32) with 45° (-LR = 0.0, 95%CI: 0.00-1.90) and 90° (-LR = 0.0, 95%CI: 0.00-0.94) having the lowest negative LR. This study indicates that the 0° hip adduction test resisted at the ankles optimizes the diagnostic procedure without compromising diagnostic capacity to identify experimental groin pain. Validation in clinical populations is warranted.

[Management of vaginal infection following failure of a probabilistic treatment: is the vaginal swab really useful?]. / Prise en charge des infections vaginales après échec d'un traitement probabiliste : le prélèvement vaginal est-il réellement utile ?

OBJECTIVE: The aim of this observational national multi-centre study was to describe medical care of vaginal infections resisting a primary probabilistic treatment. PATIENTS AND METHODS: Two hundred and seventy female patients were included during a 9-month period (from 2013, March 20th to 2013, December 7th) by 155 gynaecologists located throughout France. RESULTS: All patients were presenting a vulvo-vaginitis episode which started about three weeks ago and which was characterized by leucorrhea (93 % cases), itching (88 % cases) and/or vulvar and/or vaginal irritation (88 % cases). In most cases, this episode was previously treated by a short course of an azole antifungal medication. This treatment was initiated by the patient herself without any doctor's prescription in six out of 10 cases and had no influence on the evolution of the original clinical symptoms. Second line treatments included azole antifungal medications (56 % cases), local fixed combinations (antifungal agent and bactericidal antibiotic) (29 %), metronidazole (9 %), oral antibiotics (7.4 %). At the end of the treatment, 85 % patients recovered from vaginitis symptoms. The recovery rate was 82.6 % for patients who got a bacteriological examination and 87.6 % for patients who were treated without any bacteriological examination. The difference is not statistically significant. DISCUSSION AND CONCLUSION: These results seem to show that a probabilistic medical care is as effective as (but probably more economical than) a therapeutic strategy guided by the results of further examinations in case of failure of a primary treatment. This conclusion should be confirmed by a medico-economic comparison after randomization.

Intra-operative monitoring of the spinal accessory nerve: a systematic review.

OBJECTIVE: To investigate evidence that intra-operative nerve monitoring of the spinal accessory nerve affects the prevalence of post-operative shoulder morbidity and predicts functional outcome. METHODS: A search of the Medline, Scopus and Cochrane databases from 1995 to October 2012 was undertaken, using the search terms 'monitoring, intra-operative' and 'accessory nerve'. Articles were included if they pertained to intra-operative accessory nerve monitoring undertaken during neck dissection surgery and included a functional shoulder outcome measure. Further relevant articles were obtained by screening the reference lists of retrieved articles. RESULTS: Only three articles met the inclusion criteria of the review. Two of these included studies suggesting that intra-operative nerve monitoring shows greater specificity than sensitivity in predicting post-operative shoulder dysfunction. Only one study, with a small sample size, assessed intra-operative nerve monitoring in neck dissection patients. CONCLUSION: It is unclear whether intra-operative nerve monitoring is a useful tool for reducing the prevalence of accessory nerve injury and predicting post-operative functional shoulder outcome in patients undergoing neck dissection. Larger, randomised studies are required to determine whether such monitoring is a valuable surgical adjunct.

[Multicentric prospective randomized study evaluating the interest of intravaginal electro-stimulation at home for urinary incontinence after prior perineal reeducation. Interim analysis]. / Étude prospective multicentrique randomisée évaluant l'intérêt de l'électrostimulation intravaginale à domicile après rééducation périnéale pour incontinence urinaire. Analyse intermédiaire.

OBJECTIVES: Perineal reeducation of stress urinary incontinence is beneficial in 80% of cases. However, patients have to perform self-retraining exercises of the perineal muscles at home, in order to maintain the benefit of the physiotherapy. The aim of this study is to assess the benefit of GYNEFFIK(®), a perineal electro-stimulator, during this home-care phase. PATIENTS AND METHODS: Women with stress urinary incontinence (UI) or with mixed UI (composed predominantly of stress UI) that responded to physiotherapy were included in this study in two parallel groups. The groups followed a self-reeducation program, with or without GYNEFFIK(®) electro-stimulation sessions. The comparison of the two groups was based on the rate of women for whom the benefit of the initial perineal reeducation was maintained (defined as non-worsening ICIQ and Ditrovie scales' score). RESULTS: According to the protocol, an interim analysis was performed on 95 patients (i.e. almost half of the expected sample size) who had had at least one evaluation under treatment, among which 44 patients had finished the study. The therapeutic benefit of the initial perineal reeducation was maintained in 87.8% of the GYNEFFIK(®) patient group, while it was maintained in 52.2% (P=0.0001) in the usual care group (i.e. who did not use electro-stimulation). DISCUSSION AND CONCLUSION: Likewise, patient had a more favorable subjective impression when using GYNEFFIK(®) (83.7% versus 60.0% in the usual care group) as they felt that they improved during the study. In the GYNEFFIK(®) group, no increase in symptoms was reported, whereas almost one out of five patients in the usual care group felt that their condition had worsened.

Lymphoedema following treatment for head and neck cancer: impact on patients, and beliefs of health professionals.

Cervicofacial lymphoedema is a recognised side-effect that may result following treatment for head and neck cancer. This study aimed to investigate the perspectives of affected patients and the beliefs that treating health professionals hold about head and neck lymphoedema. Ten patients with head and neck lymphoedema and 10 health professionals experienced in the treatment of head and neck cancer patients agreed to participate in semi-structured face to face interviews. Interviews were recorded, audio files were transcribed and coded and then analysed for themes. Themes of experiences of patients with head and neck lymphoedema and the beliefs of health professionals largely overlapped. Given its visible deformity, the main effect of lymphoedema in head and neck cancer patients was on appearance. In some cases this lead to negative psychosocial sequelae such as reduced self-esteem, and poor socialisation. Clinicians need to be aware of those patients more likely to experience lymphoedema following treatment for head and neck cancer, and how they are affected. Understanding how patients with facial lymphoedema are affected psychologically and physically, and the importance of prompt referral for lymphoedema treatment, might ultimately improve outcomes and ensure optimal management.

[Management strategies for major depressive episodes as a function of initial response to an SSRI or SNRI antidepressant: results of the ORACLE survey]. / Stratégie de prise en charge d'un EDM en fonction de la réponse précoce à un antidépresseur IRS ou IRSNA: résultats de l'enquête ORACLE.

OBJECTIVE: The main aim of the major depressive episode treatment is to obtain a complete remission. However, partial remission (persistence of residual symptoms) is a frequent outcome of major depressive episodes, concerning approximately half of the patients who were responders to the treatment. An inadequate treatment response after three weeks of treatment is considered by the ANAES recommendations as a potential reason to modify the treatment regimen. The primary objectives of this survey were to describe the therapeutic strategies implemented in subjects treated as outpatients for a major depressive episode following evaluation of the initial response to an SSRI or an SNRI antidepressant and to assess by a naturalistic way the impact of these strategies on the extent of remission at three months. The secondary objective was to determine, by multivariate analysis, others factors able to influence the remission. METHODS: This prospective observational survey concerned 2 138 patients treated by community psychiatrists (n=582) and presenting a major depressive episode in the context of a recurrent depressive disorder. Patients were assessed at inclusion and at Weeks 3, at Week 6 and at Week 12. Changes in score on the Hamilton Depression Scale (Ham-D) and CGI severity between inclusion and Week 3 and improvement scores were evaluated. The therapeutic strategies after evaluation were described. Remission was defined as a score of 1 or 2 on the CGI-improvement scale; a treatment response at Week 3 was defined as a decrease of at least 50% in the Ham-D score. The physician also provided an overall rating of satisfaction with the treatment at Week 3. RESULTS: Data from 1 974 patients were analysed. The mean age at inclusion was 42.7 years, 70% of the patients were women; the mean age at first episode was 32.2 years, the average time since the last episode was 3.6 years. The mean Ham-D score at inclusion was 23.6 +/- 5.8. At Week 3, 29.1% of patients were considered treatment responders. The antidepressant dose was subsequently increased in 10.2% of responders compared to 36.3% of non-responders. When the physician rated the treatment response as unsatisfactory, the dose was increased in 56% of cases. At week 12, 83.7% of patients were in remission as defined by the CGI; according to physician judgement, 45.7% were in complete remission and 43.3% in partial remission. According to the literature, the existence of an early response to the treatment predicted a total remission at Week 12 (69.1% of the treatments responders at Week 3 were in complete remission at Week 12, vs 35.7% of the treatments not-responders). CONCLUSION: These results underline the professional practices in private community psychiatric practice in France. At Week 3, posology increased for only 36.3% of the patients, whereas it is one of the therapeutic strategies recommended by the ANAES. Participating physicians relied on their subjective judgement about initial treatment response when making decisions about treatment strategies rather than by psychometric scores. At Week 3, 29.1% of patients were considered treatment responders according to the change in Ham-D score, compared to 57.3% whose treatment response was considered satisfactory by the physician. The decision to increase the dose was more closely associated with subjective perceptions of satisfaction than with psychometric rating scale scores, despite psychometric evaluation was systematic in the ORACLE survey, what is not the case in usual practice in France, except for clinical research. In addition, this study confirms an important data for the clinician: there is a correlation between early response to the treatment (Week 3) and complete remission at the end of the acute phase of treatment (Week 12).

Three-dimensional structure of the Hospital Anxiety and Depression Scale in a large French primary care population suffering from major depression.

Few studies have been specifically carried out to characterize the dimensional structure of the Hospital Anxiety and Depression Scale (HADS) and those that have, have yielded contradictory results. We have examined the factor structure and sensitivity to change of the HADS in a large French outpatient primary care population treated with sertraline for major depression (DSM-IV criteria). Factor analysis of the HADS was performed in 2669 outpatients and in subsamples using a principal component procedure with Varimax rotation. Concurrent change sensitivity of the HADS was compared with that for the Hamilton Depression Rating Scale (HDRS) after at least 45 days of sertraline treatment. Three distinct factors emerged from the HADS factor analysis: a "depression" factor and two separate anxiety subscales: "psychic anxiety" and "psychomotor agitation" whose mean reductions in scores from baseline were significantly correlated (0.36-0.45) with the reduction of the HDRS baseline score. These new data provide support for the use of the HADS's three-dimensional structure to measure improvement of selected symptoms of anxiety during antidepressant therapy.

Economic costs of urinary incontinence in community-dwelling Australian women.

OBJECTIVE: To estimate the economic cost of urinary incontinence in community-dwelling Australian women aged 18 years and over for the year 1998. DESIGN: Extrapolation of data from studies of women with incontinence to the Australian population of women aged 18 years and over in 1998. MAIN OUTCOME MEASURES: Estimated prevalence of urinary incontinence in 1998, and estimated cost in Australian dollars of resource use and personal costs related to management of incontinence. RESULTS: An estimated 1835628 community-dwelling women over the age of 18 years had urinary incontinence in 1998. The total annual cost of this urinary incontinence is estimated at $710.44 million, or $387 per incontinent woman, comprising $338.47 million in treatment costs and $371.97 million in personal costs. An estimated 60% of women with incontinence in 1998 were aged 40 years or over. Assuming the prevalence of incontinence remains constant and, allowing for inflation, we project that the total annual cost in 20 years' time will be $1267.85 million, 93% ($1.18 billion) of which will constitute costs associated with women aged over 40 years. CONCLUSIONS: Urinary incontinence imposes a considerable drain on Australian healthcare resources. More research is needed to understand the magnitude of the problem and potential gains from continence promotion.

Immobilization of oligonucleotides on crosslinked poly(vinyl alcohol) for application in DNA chips.

In biotechnological applications there is an enormeous growth in the development of new miniaturized devices to reduce timescales, cost and amounts of reagents and starting materials. DNA chips represent miniaturized analytical tools that allow the simultaneous detection of different targets for high throughput screening. They consist of a small size support on which DNA probes are in-situ synthezised or immobilized. We present protocols for the effective immobilization of pre-synthezised 16S rRNA oligonucleotides on crosslinked poly(vinyl alcohol) (PVA). The polymeric gel consists of poly(vinyl alcohol) (PVA) crosslinked with poly(allylamin chloride) (PALAM) and monochlortriazinyl-beta-cyclodextrin (beta-CD) at pH 4,6.8,8 and 9. Mechanical characterization of the gels show that the immobilization capacity increases with increasing pH and increasing crosslinking within the gel. We will demonstrate that the hybridization efficiency on PVA chips is superior over commercially available chips based on nylon, nitrocellulose and aminoalkylsilane.

[Epidemiology and management of suspected pneumonia in nursing home residents]. / Epidémiologie et prise en charge des pneumopathies suspectées en maison de retraite.

OBJECTIVE: We conducted a descriptive epidemiology study to examine the conditions of management of infectious lung disease in institutionalized elderly populations (population profile, diagnostic and therapeutic modalities) and to analyze the general and mental consequences in terms of independence (impact of the infectious event on the subject's life style). PATIENTS AND METHODS: A pragmatic survey was conducted by a multicentric observatory composed of 573 general practitioners, practicing in nursing homes. The series included 1790 patients aged over 70 years and residing in nursing homes who developed infectious lung disease over a 10-month period. The MMSE score was used to assess mental status and the Barthel index to assess functional handicap. Each patient was evaluated at the time of the final diagnosis (prescription of an antibiotic or decision for hospitalization) and at most 3 days after the end of this treatment or at discharge from hospital. RESULTS: The elderly population (84 +/- 7 years) was predominantly composed of women. The patients were treated for an acute respiratory infection considered in 30% of the cases to be acute lobar pneumonia. Subgroups of patients were identified for analysis: death (3.7%), x-ray confirmation of the diagnosis (11.5%), hospitalized patients (10.2%). In addition to major deterioration of the general health status, a consequence of the infection more than of the severity of the respiratory symptoms, the development of an acute episode coincided with reduced intellectual functions and onset of a state of confusion. In 70% of the cases, this resulted in a loss of independence of variable importance--simple difficulty for moving around to major functional handicap. The infectious episode was cured or improved (persistence of minor signs not requiring specific treatment) in 94.3% of the cases with appropriate antibiotics: single-drug regimen in 93.7% give per os (75%) or intravenously (25%) using aminopenicillin (with or without a beta lactamase inhibitor) in 80% of the cases. Antibiotic treatment was associated with physical therapy in more than half the cases, and with general conticosteroids in 40%. The treatment scheme was modified in 9.4% of the cases (change of antibiotic in 6%). CONCLUSION: This survey confirms the high risk related to general conditions in elderly institutionalized patients who develop respiratory infection. More than the infection itself, the rapid degradation of the general health status, or decompensation of comorbid states can create life-threatening situations or favor the development of irreversible handicaps.

Constipation in Australian women: prevalence and associated factors.

A postal health survey was completed by 14761 young women (aged 18-23 years), 14070 middle-aged women (45-50 years) and 12893 older women (70-75 years). The prevalence of constipation was 14.1% (CI 13.5-14.7) in young women, 26.6% (CI 25.9-27.4) in middle-aged women, and 27% (CI 26.9-28.5) in the older women. The prevalence of hemorrhoids was 3.2% (CI 2.9-3.4 young), 17.7% (CI 17.1-18.4 middle-aged) and 18.3% (CI 17.6-19.0 older). In the middle-aged and older women, those who reported previous gynecologic surgery were between 18% and 63% more likely to report constipation; in the younger cohort, women with one or two children were also more likely to report constipation (adjusted OR 1.43-1.46). One-third of the young women and half the middle-aged and older women had sought help for constipation; the majority indicated that they were satisfied with the help available to them.

Leaking urine: prevalence and associated factors in Australian women.

The Women's Health Australia project provided the opportunity to examine the prevalence of leaking urine and associated variables in three large cohorts of Australian women 18-23 years of age ("young" N = 14,761), 45-50 ("mid-age" N = 14,070), and 70-75 ("older" N = 12, 893). The proportion of women reporting leaking urine was 12.8% (95% CI: 12.2-13.3), 36.1% (35.2- 37.0), and 35% (34.1- 35.9) in each of the three cohorts, respectively. Logistic regression analysis showed significant associations between leaking urine and parity in the young and mid-age women, and between leaking urine and constipation, other bowel symptoms, body mass index, and urine that burns or stings in all three groups. In the mid-age and older cohorts, women who reported having both hysterectomy and prolapse repair, or prolapse repair alone, were also more likely to report leaking urine. Lower scores on the physical and mental component summary scores of the medical outcomes survey short form (36 items) questionnaire suggest lower quality of life among women who report leaking urine, compared with those who do not. Neurourol. Urodynam. 18:567-577, 1999.

Leaking urine in Australian women: prevalence and associated conditions.

The paper aims to (1) assess the prevalence of leaking urine and to (2) explore associations between leaking urine and a variety of other symptoms, conditions, surgical procedures and life events in three large cohorts of Australian women, who are participants in the Australian Longitudinal Study on Women's Health. Young women aged 18-23 (N = 14,000), mid-age women, 45-50 (N = 13,738) and older women, 70-75 (N = 12,417), were recruited randomly from the national HIC/Medicare database. Leaking urine was reported by approximately one in eight young women [estimated prevalence 12.8% (95% CI: 12.2-13.3)] and one in three mid-age women [36.1% (CI: 35.2-37.0)] and older women [35.0% (CI: 34.1-35.9)]. Leaking urine was significantly associated with parity, conditions which increase the pressure on the pelvic floor such as constipation and obesity, past gynecological surgery and conditions which can impact on bladder control. The study showed that fewer than half the women had sought help for the problem and that younger women were less likely to be satisfied with the help available for this problem. Strategies for continence promotion, including opportunistic raising of the issue at the time of cervical screening and pregnancy care are suggested, so that the health and social outcomes of untreated chronic incontinence in women might be improved.

Postpartum perineal management and best practice.

Sutured damage to the perineum occurs in at least 39% of women being delivered in Australia and perineal wound breakdown is associated with perineal oedema. The available literature was reviewed to ascertain what might constitute best practice for postpartum perineal wound management. Classification of levels of evidence was used to prioritise the available evidence. Little evidence that might be considered scientifically robust was found. Recommendations based on the available levels of evidence include a careful emphasis on perineal hygiene, cryotherapy, elevation of the foot of the bed in the presence of perineal oedema and regularly performed pelvic floor exercises.

Incontinence during pregnancy. Prevalence and opportunities for continence promotion.

A cross-sectional study using a structure interview was conducted with 304 women in the postnatal ward of a large NSW teaching hospital. Women were asked about any incontinence experienced in the last month of pregnancy, and about advice and interventions for bladder control or incontinence they had received during pregnancy. Sixty four per cent of women reported incontinence during pregnancy. Compared to women with no prior deliveries, those with a previous forceps delivery were 10 times more likely to experience incontinence, and with prior vaginal deliveries 4 times more likely to experience incontinence. Women who reported experiencing bouts of coughing on a regular basis during pregnancy were 4 times more likely to experience incontinence than those who did not. While 68% of the women reported being examined vaginally at least once during pregnancy, only 6% of the sample reported having their pelvic floor muscles tested during routine vaginal examination. Twenty three per cent of women reported having spoken with a healthcare professional regarding loss of bladder control. The results indicate that opportunities for continence promotion are not being utilized.

[Comparison of different methods in the assessment of the ratio of hypertensive patients responding to antihypertensive treatment]. / Comparaison de différentes méthodes d'évaluation des taux de répondeurs à un traitement antihypertenseur, chez les patients hypertendus.

Identification of a responder to an antihypertensive treatment is helpful and also very difficult in an open uncontrolled study. The existence of many arbitrary methods to define a responder, the placebo effect and the regression to the mean phenomenon coexist and give spurious interpretation. We analysed an open study recruiting 6,530 hypertensive patients (DBP > or = 95 mmHg at entry), treated with the same antihypertensive drug during 3 months. Mean initial and at 3 months blood pressures were respectively 178/101 mmHg and 151/86 mmHg. We observed significant variation in the % of responders (20 to 80%) to a drug when applying different methods. Placebo effect and regression to the mean lead to an overestimation. Without a placebo controlled design, we suggest to increase the BP level for inclusion to determine the % of responders with the standard goal pressure (DBP < 90 mmHg) and to use Oldham's method for adjusting for the regression to the mean unless the coefficient of correlation found is around zero and if upper level of DBP is not selected for inclusion.

Identification of a novel, N7-deoxyguanosine adduct as the major DNA adduct formed by a non-bay-region diol epoxide of benzo[a]pyrene with low mutagenic potential.

A metabolite of benzo[a]pyrene, 9-r,10-t-dihydroxy-7,8-c-oxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE-III), that is not thought to be involved in carcinogenesis has nevertheless been shown to bind extensively to DNA in vitro. The adducts formed by this non-bay-region diol epoxide in Chinese hamster ovary cells are much less mutagenic than those formed by an isomeric diol epoxide that is carcinogenic. We have isolated and characterized three major adducts formed by in vitro reaction of BPDE-III with DNA. The major adduct, accounting for over half of the total is formed by reaction of BPDE-III with the N7 position of dGuo and is recovered after enzymatic digestion as an N7-Gua adduct. A second major adduct involves the N2 position of dGuo, while the third adduct is tentatively identified as a C8-substituted dGuo. Little or no reaction with deoxyadenosine residues is detected. The N7 adduct is unstable in DNA at 37 degrees C and is released as the modified base with a half-life of about 24 h. This adduct lability apparently leads to single-strand breaks and alkali-sensitive sites in the DNA and may account in part for some of the biological properties of BPDE-III adducts. This represents the first description of an N7-dGuo adduct that is formed in DNA as the major adduct by a diol epoxide derived from a carcinogenic polycyclic aromatic hydrocarbon.