[Secondary surgery of breast reconstructions by breast implant. Assessment of patient satisfaction based on surgical technique implant conservation vs. autologous conversion]. / Chirurgie secondaire des reconstructions mammaires par prothèses. Évaluation de la satisfaction des patientes selon la technique chirurgicale : conservation d'implant vs conversion autologue.

INTRODUCTION: Breast reconstruction with implants has long-term disadvantages and is leading an increasing number of patients to request secondary corrective surgery. Two surgical strategies are possible: implant replacement (associated with capsulectomy/capsulotomy and/or lipofilling procedures) and implant removal associated with the provision of autologous tissue (flap and/or lipofilling). METHOD: Between 2010 and 2018, 54 patients underwent secondary surgery for correction of a first implant breast reconstruction. The reasons for dissatisfaction with the initial reconstruction, the procedures performed, and postoperative complications were analysed. Patient well-being and satisfaction were evaluated using the BREAST-Q questionnaire. RESULTS: Thirty-four patients benefited from a prosthesis change and 20 patients benefited from a permanent removal of their prosthesis combined with the addition of autologous tissue. The presence of a periprosthetic shell, pain, fixed appearance of the breast and breast asymmetry were the most frequent reasons for dissatisfaction. With a mean follow-up of 2.6 years, autologous conversion patients were generally more satisfied with the appearance of their breasts than patients who retained a breast implant (P<0.0001). CONCLUSION: In cases of poor esthetic or functional outcomes of implant-based breast reconstruction, removal of the prosthesis in combination with autologous reconstruction provides better results in terms of well-being and satisfaction than implant replacement.

Consideration of the likely benefit from implementation of prostate image-guided radiotherapy using current margin sizes: a radiobiological analysis.

OBJECTIVE: To estimate the benefit of introduction of image-guided radiotherapy (IGRT) to prostate radiotherapy practice with current clinical target volume-planning target volume (PTV) margins of 5-10 mm. METHODS: Systematic error data collected from 50 patients were used together with a random error of σ=3.0 mm to model non-IGRT treatment. IGRT was modelled with residual errors of Σ=σ=1.5 mm. Population tumour control probability (TCP(pop)) was calculated for two three-dimensional conformal radiotherapy techniques: two-phase and concomitant boost. Treatment volumes and dose prescriptions were ostensibly the same. The relative field sizes of the treatment techniques, distribution of systematic errors and correlations between movement axes were examined. RESULTS: The differences in TCP(pop) between the IGRT and non-IGRT regimes were 0.3% for the two-phase and 1.5% for the concomitant boost techniques. A 2-phase plan, in each phase of which the 95% isodose conformed to its respective PTV, required fields that were 3.5 mm larger than those required for the concomitant boost plan. Despite the larger field sizes, the TCP (without IGRT) in the two-phase plan was only 1.7% higher than the TCP in the concomitant boost plan. The deviation of craniocaudal systematic errors (p=0.02) from a normal distribution, and the correlation of translations in the craniocaudal and anteroposterior directions (p<0.0001) were statistically significant. CONCLUSIONS: The expected population benefit of IGRT for the modelled situation was too small to be detected by a clinical trial of reasonable size, although there was a significant benefit to individual patients. For IGRT to have an observable population benefit, the trial would need to use smaller margins than those used in this study. Concomitant treatment techniques permit smaller fields and tighter conformality than two phases planned separately.

Unacceptable side-effects associated with a hyperosmolar vaginal microbicide in a phase 1 trial.

We carried out a phase 1 trial of a candidate vaginal microbicide gel against HIV-1 and other sexually transmitted diseases, which contained cellulose acetate 1,2-benzenedicarboxylate (also known as cellulose acetate phthalate) in a glycerol-based vehicle. We had to terminate the study after five women had completed dosing, due to all women experiencing unacceptable vulvo-vaginal side-effects. Further investigations showed that the gel had a very high osmolality, which we believe led to excessive fluid transudation across the vaginal mucosa and acute mucosal dysfunction. We also showed that the rheology of the gel changed dramatically on fluid dilution. The osmolality and rheology of candidate microbicides and other genital mucosal products should therefore be analysed and considered at an early stage of product development.

Practical aspects of implementation of helical tomotherapy for intensity-modulated and image-guided radiotherapy.

AIMS: Image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) represent two important technical developments that will probably improve patient outcome. Helical tomotherapy, provided by the TomoTherapy HiArt system, provides an elegant integrated solution providing both technologies, although others are available. Here we report our experience of clinical implementation of daily online IGRT and IMRT using helical tomotherapy. MATERIALS AND METHODS: Methods were needed to select patients who would probably benefit. Machine-specific commissioning, a quality assurance programme and patient-specific delivery quality assurance were also needed. The planning target volume dose was prescribed as the median dose, with the added criterion that the 95% isodose should cover 99% of the target volume. Although back-up plans, for delivery on conventional linear accelerators, were initially prepared, this practice was abandoned because they were used very rarely. RESULTS: In the first 12 months, 114 patients were accepted for treatment, and 3343 fractions delivered. New starts averaged 2.6 per week, with an average of 17.5 fractions treated per day, and the total number capped at 22. This has subsequently been raised to 24. Of the first 100 patients, 96 were treated with radical intent. Five were considered to have been untreatable on our standard equipment. IGRT is radiographer led and all patients were imaged daily, with positional correction made before treatment, using an action level of 1mm. A formal training programme was developed and implemented before installation. The in-room time fell significantly during the year, reflecting increasing experience and a software upgrade. More recently, after a couch upgrade in April 2009, the mean in-room time fell to 18.6 min. CONCLUSIONS: Successful implementation of tomotherapy was the result of careful planning and effective teamwork. Treatment, including daily image guidance, positional correction and intensity-modulated delivery, is fast and efficient, and can be integrated into routine service. This should encourage the adoption of these technologies.

Alcoholism and neuropeptides: an update.

As with other addictions, human alcoholism is characterised as a chronically relapsing condition. Consequently, the "holy grail" from a therapeutic viewpoint is the development of clinically effective, safe drugs that promote high compliance rates and prevent relapse. Here we discuss the potential of therapeutics targeting neuropeptide systems implicated in aberrant alcohol-seeking behaviour. Clearly, much of the data so far available comes from pre-clinical studies; however, one of the first effective therapeutic strategies for alcoholism (still in use today) was the use of non-selective opioid receptor antagonists, such as naltrexone (Revia). In addition to opioid receptors, other neuropeptide receptors including those for corticotrophin releasing factor (CRF), neuropeptide Y and nociceptin may represent valid therapeutic targets to regulate alcohol consumption and the affective consequences of alcohol withdrawal.

Vasoconstrictive effects of endothelin-1, endothelin-3, and urotensin II in isolated perfused human lungs and isolated human pulmonary arteries.

BACKGROUND: Urotensin II (UII) has been identified as a ligand for the orphan receptor GPR14 through which it elicits potent vasoconstriction in humans and non-human primates. The pulmonary vasculature is particularly sensitive; human UII (hUII) exhibits a potency 28 times that of endothelin (ET)-1 in isolated pulmonary arteries obtained from cynomolgus monkeys. However, hUII induced vasoconstriction in isolated human intralobar pulmonary arteries is variable, possibly as a result of location dependent differences in receptor density or because it is only uncovered by disease dependent endothelial dysfunction. METHODS: The vasoactivity of both hUII and gobi UII (gUII) in comparison with ET-1 and ET-3 was studied in isolated perfused lung preparations (n = 14) and isolated intralobar pulmonary arteries (n = 40, mean diameter 548 (27) microm) obtained from 17 men of mean (SE) age 67 (2) years and eight women of mean (SE) age 65 (3) years with a variety of vascular diseases. RESULTS: ET-1 (10 pM-100 nM) and ET-3 (10 pM-30 nM) elicited vasoconstriction in the lung preparations, inducing comparable increases in pulmonary arterial pressure of 24.8 (4.5) mm Hg and 14.5 (4.9) mm Hg, respectively, at 30 nM (p = 0.13). Similarly, ET-1 (10 pM-300 nM) and ET-3 (10 pM-100 nM) caused marked vasoconstriction in isolated pulmonary arteries, inducing maximal changes in tension of 4.36 (0.26) mN/mm and 1.54 (0.44) mN/mm, respectively, generating -logEC(50) values of 7.67 (0.04) M and 8.08 (0.07) M, respectively (both p<0.05). However, neither hUII nor gUII (both 10 pM-1 micro M) had any vasoactive effect in either preparation. CONCLUSION: UII does not induce vasoconstriction in isolated human pulmonary arterial or lung preparations and is therefore unlikely to be involved in the control of pulmonary vascular tone.

Chromosomal analysis of non-small-cell lung cancer by multicolour fluorescent in situ hybridisation.

The cytogenetic abnormalities in non-small-cell lung cancer remain elusive due primarily to the difficulty in obtaining metaphase spreads from solid tumours. We have used the molecular cytogenetic techniques of multicolour fluorescent in situ hybridisation (M-FISH) and comparative genomic hybridisation (CGH) to analyse four primary non-small-cell lung cancer samples and two established cell lines (COR-L23 and COR-L105) in order to identify common chromosomal aberrations. CGH revealed regions on 5p, 3q, 8q, 11q, 2q, 12p and 12q to be commonly over-represented and regions on 9p, 3p, 6q, 17p, 22q, 8p, 10p, 10q and 19p to be commonly under-represented. M-FISH revealed numerous complex chromosomal rearrangements. Translocations between chromosomes 5 and 14, 5 and 11 and 1 and 6 were observed in three of the six samples, with a further 14 translocations being observed in two samples each. Loss of the Y chromosome and gains of chromosomes 20 and 5p were also frequent. Chromosomes 4, 5, 8, 11, 12 and 19 were most frequently involved in interchromosomal translocations. Further investigation of the recurrent aberrations will be necessary to identify the specific breakpoints involved and any role they may have in the aetiology, diagnosis and prognosis of non-small-cell lung cancer.

Neurobehavioral effects of alcohol in AMPA receptor subunit (GluR1) deficient mice.

Of the ionotropic glutamatergic receptors, the NMDA receptor is clearly implicated in the acute and chronic effects of ethanol; however, the role of the AMPA receptor in mediating the effects of ethanol in vivo is as yet unclear. Using mice deficient in the AMPA receptor subunit GluR1 (GluR1-/- mice), we investigated whether the AMPA receptor had a significant role in mediating the effects of ethanol. GluR1-/- mice showed greater locomotor activity in a novel environment, but by the fifth day of repeated testing their activity was the same as that of wild-type mice. In contrast to their enhanced locomotor activity, on an accelerating rotarod GluR1-/- mice performed consistently worse than wild-types. With regard to the effects of ethanol on motor responses, GluR1-/- mice did not differ significantly from wild-type mice in ethanol's sedative or incoordinating effects. However, the GluR1-/- mice were insensitive to the hypothermic effects of a hypnotic dose of ethanol in contrast to wild-types; this effect was dissociable from the hypnotic effects of ethanol. Further, tolerance to ethanol developed equally for GluR1-/- mice versus wild-type mice. In terms of alcohol drinking behavior, compared to wild-types, GluR1-/- mice differed neither in the acquisition of voluntary ethanol consumption nor in stress-induced ethanol drinking, nor in the expression of an alcohol deprivation effect (ADE) which is used as a model of relapse-like drinking behavior. In summary, although the loss of a hypothermic effect of ethanol in GluR1-/- mice indicates a critical role for the AMPA receptors in this effect, the GluR1 subunit of the AMPA receptor does not seem to play a critical role in the etiology of alcohol dependence. However, changes observed in activity patterns may be related to the putative role of AMPA receptors in attention deficit hyperactivity disorder.

Validation of four different risk stratification systems in patients undergoing off-pump coronary artery bypass surgery: a UK multicentre analysis of 2223 patients.

BACKGROUND: Various risk stratification systems have been developed in coronary artery bypass graft surgery (CABG), based mainly on patients undergoing procedures with cardiopulmonary bypass. OBJECTIVE: To assess the validity and applicability of the Parsonnet score, the EuroSCORE, the American College of Cardiology/American Heart Association (ACC/AHA) system, and the UK CABG Bayes model in patients undergoing off-pump coronary artery bypass surgery (OPCAB) in the UK. METHODS: Data on 2223 patients who underwent OPCAB in eight cardiac surgical centres were collected. Predicted mortality risk scores were calculated using the four systems and compared with observed mortality. Calibration was assessed by the Hosmer-Lemeshow (HL) test. Discrimination was assessed using the receiver operating characteristic (ROC) curve area. RESULTS: 30 of 2223 patients (1.3%) died in hospital. For the Parsonnet score the HL test was significant (p < 0.001) and the receiver operating characteristic curve (ROC) area was 0.74. For the EuroSCORE the HL test was also significant (p = 0.008) and the ROC area was 0.75. For the ACC/AHA system the HL test was non-significant (p = 0.7) and the ROC area was 0.75. For the UK CABG Bayes model the HL test was also non-significant (p = 0.3) and the ROC area was 0.81. CONCLUSIONS: The UK CABG Bayes model is reasonably well calibrated and provides good discrimination when applied to OPCAB patients in the UK. Among the other three systems, the ACC/AHA system is well calibrated but its discrimination power was less than for the UK CABG Bayes model. These data suggest that the UK CABG Bayes model could be an appropriate risk stratification system to use for patients undergoing OPCAB in the UK.

Chromosomal alterations in small cell lung cancer revealed by multicolour fluorescence in situ hybridization.

Small cell lung cancer (SCLC) is a major cause of cancer related morbidity and mortality. Karyotypic studies have revealed numerous chromosomal aberrations in most SCLC however, classical G-banding analysis is unable to fully characterise complex marker chromosomes. Recent developments in molecular cytogenetics now allow accurate identification of the chromosomal components of complicated rearrangements. We have applied the technique of multicolour fluorescence in situ hybridization (M-FISH) in combination with comparative genomic hybridization (CGH) to the analysis of 5 SCLC cell lines and 1 primary tumour specimen to characterise the chromosomal abnormalities. CGH analysis identified many similarities between specimens, with frequent DNA copy number decreases on chromosomes 3p, 5q, 10, 16q, 17p and frequent gains on 3q, 1p, 1q and 14q. In contrast, M-FISH analysis revealed a large number of structural abnormalities, with each specimen demonstrating an individual pattern of chromosomal translocations. Forty different translocations were identified with the vast majority (39) being unbalanced. Chromosome 5 was the most frequently rearranged chromosome (9 translocations) followed by chromosomes 2, 10 and 16 (6 translocations each). Further investigation of these frequently involved chromosomes is warranted to establish whether consistent break points are involved in these translocations, causing dysregulation of specific genes that are crucial for tumour progression and secondly to identify the affected genes.

The impact of the duration of mechanical ventilation on the respiratory outcome in smokers undergoing cardiac surgery.

STUDY OBJECTIVE: To determine the impact of the duration of mechanical ventilation on the rate of pulmonary complications in smokers undergoing cardiac surgery. METHODS: Retrospective analysis of 2163 patients who underwent elective cardiac surgery between September 1993 and August 1999. Based on a 3-month preoperative smoking cessation, patients were classified as smokers, ex-smokers and non-smokers. Their postoperative pulmonary complications were compared and related to the duration of mechanical ventilation. RESULTS: Postoperative pulmonary complications were twice as common in smokers (29.5%) as non-smokers (13.6%) and ex-smokers (14.7%). Although smokers required a longer duration of mechanical ventilation, this was not statistically significant. Smokers had a higher rate of increase in postoperative pulmonary complications beyond 6 h of mechanical ventilation (P<0.002). CONCLUSION: Prolonged mechanical ventilation in active smokers undergoing cardiac surgery is associated with a significant increase in the respiratory morbidity. Surgical strategies that allow early extubation may improve the respiratory outcome in smokers.

Association analysis of HTR6 and HTR2A polymorphisms in sporadic Alzheimer's disease.

In order to identify gene variants related to the serotonergic neurotransmitter system that possibly represent a hereditary risk factor for sporadic Alzheimer's disease (AD), patients suffering from AD and non-demented psychiatric inpatients without symptoms of dementia were genotyped for polymorphisms of HTR6 (267C/T) and HTR2A (-1438G/A). Although there was a tendency toward an increased number of the genotype TT of the 5-HT6 receptor polymorphism in AD patients when compared to controls (2.8% vs. 1.3%), neither this nor the 5-HT2A promoter polymorphism showed significant differences in their genotypic or allelic distribution among patients and controls. These polymorphisms probably do not represent major genetic risk factors of AD. However, further studies including other genetic variants of the serotonergic neurotransmitter system are needed in order to elucidate their role in AD.

Right ventricular needle embolus in an injecting drug user: the need for early removal.

This case report describes an unusual cardiac complication in a 22 year old, female injecting drug user. The retention of two fractured injection needles at the site of intravenous injection in the groin, and the subsequent embolisation of one to the right ventricle, predisposed to recurrent local and systemic infections, and endocarditis. Two years later, the needle was completely embedded in the wall of the right ventricle and not suitable for transvenous removal. Removal of the retained and/or embolised needle at an earlier stage would have precluded these complications.

Alterations in central preproenkephalin mRNA expression after chronic free-choice ethanol consumption by fawn-hooded rats.

BACKGROUND: Neurotransmission mediated via opioid and dopamine receptors is believed to be involved in the reinforcing and/or rewarding effects of ethanol consumption. We previously examined the effect of ethanol consumption (and naltrexone treatment, used clinically to treat alcoholism) on micro-opioid receptor density. We describe here the effect of free-choice ethanol consumption and naltrexone treatment on preproenkephalin, preprodynorphin, and dopamine D1 and D2 receptor mRNA expression in the central nervous system. METHODS: Fawn-hooded rats were given continual free-choice access to a 5% ethanol solution or water (4 weeks) followed by 2 weeks of water alone. At the end of this abstinence period, osmotic minipumps were implanted subcutaneously to deliver saline (n = 4) or naltrexone (n = 4; 8.4 mg/kg/day for 4 weeks). After recovery from surgery, the rats again were given access to 5% ethanol under the same free-choice conditions (4 weeks). A third group of age-matched controls drank only water during the behavioral trial. At the end of the behavioral trial, the rats were decapitated, and a quantitative examination of peptide precursor mRNAs was made by using in situ hybridization histochemistry. RESULTS: Naltrexone treatment significantly decreased preprodynorphin expression in the nucleus accumbens, but neither naltrexone treatment nor ethanol consumption significantly affected dopamine D1 and D2 receptor mRNA expression. In contrast, ethanol consumption increased preproenkephalin mRNA in the central and intercalated nuclei of the amygdala but decreased preproenkephalin mRNA in the nucleus accumbens and olfactory tubercle. The decreased level of preproenkephalin mRNA in the nucleus accumbens may reflect a neuroadaptive response to increased release of dopamine, whereas the increased level of preproenkephalin mRNA in the central nucleus of the amygdala may be associated with an anxiolytic effect of ethanol consumption. CONCLUSIONS: The data support the putative role of opioid peptides in the effects of ethanol and suggest that the nucleus accumbens and central nucleus of the amygdala are loci for the reinforcing effects of ethanol.

The use of 2D and 3D displays for shape-understanding versus relative-position tasks.

Research on when and how to use three-dimensional (3D) perspective views on flat screens for operational tasks such as air traffic control is complex. We propose a functional distinction between tasks: those that require shape understanding versus those that require precise judgments of relative position. The distortions inherent in 3D displays hamper judging relative positions, whereas the integration of dimensions in 3D displays facilitates shape understanding. We confirmed these hypotheses with two initial experiments involving simple block shapes. The shape-understanding tasks were identification or mental rotation. The relative-position tasks were locating shadows and determining directions and distances between objects. We then extended the results to four experiments involving complex natural terrain. We compare our distinction with the integral/separable task distinction of Haskel and Wickens (1993). Applications for this research include displays for air traffic control, geoplots for military command and control, and potentially, any display of 3D information.

An unusual combination of diaphragmatic hernias in a patient presenting with the clinical features of restrictive pulmonary disease: report of a case.

The combination of a Morgagni hernia and a paraesophageal hernia in adults is very rarely encountered in clinical practice. In fact, to our knowledge, only three cases of this condition, which is probably a coincidental occurrence, have been reported in the medical literature. We discuss the management of a 74-year-old man found to have combined Morgagni and paraesophageal hernia who presented with clinical features of a restrictive pulmonary disease.

Pharmaceutical cost growth under capitation: a case study.

Rising drug spending has generated concern among purchasers and policymakers. This paper compares drug cost growth in a capitated system with that in managed care systems that generally did not place physicians directly at risk for drug spending. We focus on cost growth because a substantial body of literature indicates that managed care interventions that reduce the level of costs may not influence the rate of cost growth. Drug cost growth under capitation initially was below that of other systems but still above targeted rates. Over time the capitation rates rose, the amount of risk transferred to physicians declined, and spending growth accelerated.

Assessing quality of life in men with clinically localized prostate cancer: development of a new instrument for use in multiple settings.

BACKGROUND: Quality of life in prostate cancer patients with clinically localized disease has become the focus of increasing attention over the past decade. However, few instruments have been developed and validated to assess quality of life specifically in this patient population. OBJECTIVE: The purpose of this investigation was to create a comprehensive, multi-scale quality of life instrument that can be tailored to the needs of the clinician/investigator in multiple settings. DESIGN, SUBJECTS, AND MEASURES: Patients diagnosed with clinically localized prostate cancer were mailed a questionnaire consisting of new and previously validated quality of life items and ancillary scales. Data from returned questionnaires were analyzed and used to create a multiscale instrument that assesses the effects of treatment and disease on urinary, sexual, and bowel domains, supplemented by a scale assessing anxiety over disease course/effectiveness of treatment. The instrument was then mailed to a second sample of prostate cancer patients once and then again two weeks later to assess test retest reliability. To assess feasibility in clinical settings, the instrument was self-administered to a third patient sample during a urology clinic visit. RESULTS: All scales exhibited good internal consistency and test retest reliability, convergent and discriminant validity, and significant correlations with disease specific, generic health-related, and global measures of quality of life. Men with greater physiologic impairment reported more limitations in role activities and more bother. Scales were also able to differentiate patients undergoing different therapies. All scales exhibited negligible correlations with a measure of socially desirable responding. Additionally, the instrument proved feasible when used as a self-administered questionnaire in a clinical setting. CONCLUSIONS: The current instrument possesses brief multi-item scales that can be successfully self-administered in multiple settings. The instrument is flexible, relatively quick, psychometrically reliable and valid, and permits a more comprehensive assessment of patients' quality of life.

The role of opioid-dopamine interactions in the induction and maintenance of ethanol consumption.

1. Alcohol is one of the most widely used recreational drugs, but also one of the most widely abused, causing vast economic, social and personal damage. 2. Several animal models are available to study the reinforcing mechanisms that are the basis of the abuse liability of ethanol. Innate differences in opioid or dopamine neurotransmission may enhance the abuse liability of ethanol, as indicated by animal and human studies. 3. Opioid antagonists have been shown to be effective, both experimentally and clinically, in decreasing ethanol consumption, presumably since ethanol induces the release of endogenous opioid peptides in vivo. However, ethanol may also stimulate the formation of opiate-like compounds, which could interact with opioid (or dopamine) receptors. Ethanol may cause changes in neurotransmission mediated via opioid receptors that determines whether alcohol abuse is more or less likely. 4. Ethanol appears to facilitate dopamine release by increasing opioidergic activity, disinhibiting dopaminergic neurons (by inhibition of GABAergic neurotransmission) via mu-opioid receptors in the ventral tegmental area (VTA) and delta-opioid receptors in the nucleus accumbens (NAcc). The effects of ethanol would be antagonised by presynaptic kappa-opioid receptors present on dopaminergic terminals in the NAcc. 5. Mesolimbic dopamine release induced by ethanol consumption seems to indicate ethanol-related stimuli are important, focussing attention on and enabling learning of the stimuli. However, studies indicate that there are redundant pathways, and neural pathways 'downstream' of the mesolimbic dopamine system, which also enable the reinforcing properties of ethanol to be mediated.