Prognostic value of coronary multidetector CT angiography in patients with an intermediate probability of significant coronary heart disease.

The aim of this study was to determine the prognostic value of coronary multidetector CT angiography (MDCTA) in patients with an intermediate pre-test probability of significant coronary artery disease (CAD). Patients who underwent 64-slice coronary MDCTA and met the selection criteria were identified and assessed for intermediate pre-test probability. Coronary MDCTA scans were preceded by calcium scoring, whereas all MDCTA scans were interrogated for the presence of plaque composition and the distribution and degree of stenosis. Significant stenosis was classified as being >50% of the luminal diameter. All patients were followed up for the occurrence of (i) cardiac death, (ii) non-fatal myocardial infarction, (iii) unstable angina requiring hospital admission and (iv) revascularisation. 138 patients were included (follow-up of 19.9 months); of these, 8 had a cardiac event (all revascularisations) and all had a positive coronary MDCTA. Patients with normal coronary arteries or non-significant stenosis suffered no cardiac events during follow-up. There were significant differences between the two groups regarding the presence of significant stenosis (p<0.001), the presence of plaque (p = 0.011) and a calcium score >10 (p = 0.003); 36.4% of patients with significant stenosis underwent revascularisation. In conclusion, this is the first UK study to investigate survival data in a population of intermediate-risk patients with no prior history of CAD who were investigated with coronary MDCTA. Coronary MDCTA can confidently rule out significant CAD in the intermediate-risk population and guide risk factor modification in patients with demonstrated coronary atheroma.

Impaired left ventricular function has a detrimental effect on image quality in multi-detector row CT coronary angiography.

AIM: To determine whether there is a relationship between left ventricular (LV) haemodynamic parameters, circulation times, and arterial contrast opacification that might affect the image quality of computed tomography (CT) coronary angiography. METHODS: Thirty-six patients were included in the study: 18 with cardiomyopathy (CM) and LV dilatation of suspected ischaemic aetiology [age 57.9+/-13.7 years, range 30-77 years; 14 male, four female; body mass index (BMI)=27.7+/-4.5, range 25.5-31.8] and 18 controls (age 62.3+/-9.4 years, range 47-89 years; 10 male, eight female; BMI 27.8+/-6.6; range 19.2-33.6). Coronary artery image quality was assessed using a three-point visual scale; contrast medium circulation times, aortic root contrast attenuation, and LV functional parameters were studied. RESULTS: Visually reduced contrast opacification impaired image quality more often in the CM group than the control group (27.4 versus 5.1%). A total of 55.6% CM patients had a contrast transit time ranging from 30-75 s; the number of "unassessable" segments increased with increasing transit time conforming to a fitted quadratic model (R2=0.74). The relationship between LV ejection fraction and contrast attenuation may also conform to a quadratic model (R2=0.71). CONCLUSION: LV haemodynamics influence coronary artery opacification using cardiac CT, and users imaging this subgroup must do so with the knowledge of this potential pitfall. The results indicate the need for further studies examining CT protocols in this clinical subgroup.

Multi-detector row CT coronary angiography in patients with cardiomyopathy -- initial single-centre experience.

AIMS: To evaluate the diagnostic accuracy of computed tomography (CT) in assessing haemodynamically significant coronary artery stenoses in patients with cardiomyopathy (CM). SUBJECTS AND METHODS: Eighteen patients with CM were approached to undergo CT coronary angiography to evaluate the use of this technique for investigating the presence of significant coronary artery disease (CAD), and also to compare the findings with catheter angiography. RESULTS: On a segment-by-segment analysis the sensitivity, specificity, positive and negative predictive values in the CM group were 66.7, 96.5, 40 and 98.8%, respectively, with 100% accuracy in "whole-patient terms". CONCLUSION: Non-invasive, 16-detector row CT coronary angiography in patients with presumed CM would seem to be a useful clinical tool for the exclusion of significant coronary artery disease. However, the presence of suboptimal contrast opacification in this patient group means that the implication of these results must be interpreted with caution.

Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms.

METHODS: The 22q13 deletion syndrome (MIM 606232) is characterised by moderate to profound mental retardation, delay/absence of expressive speech, hypotonia, normal to accelerated growth, and mild dysmorphic features. We have determined the deletion size and parent of origin in 56 patients with this syndrome. RESULTS: Similar to other terminal deletion syndromes, there was an overabundance of paternal deletions. The deletions vary widely in size, from 130 kb to over 9 Mb; however all 45 cases that could be specifically tested for the terminal region at the site of SHANK3 were deleted for this gene. The molecular structure of SHANK3 was further characterised. Comparison of clinical features to deletion size showed few correlations. Some measures of developmental assessment did correlate to deletion size; however, all patients showed some degree of mental retardation and severe delay or absence of expressive speech, regardless of deletion size. CONCLUSION: Our analysis therefore supports haploinsufficiency of the gene SHANK3, which codes for a structural protein of the postsynaptic density, as a major causative factor in the neurological symptoms of 22q13 deletion syndrome.

Objective assessment of bladder neck elevation and urethral compression at colposuspension.

OBJECTIVES: 1. To assess whether magnetic resonance imaging and intra-operative measurements are useful in assessing bladder neck elevation and urethral compression at colposuspension; 2. to see if intra-operative measurements could be a substitute for magnetic resonance scan measurements. DESIGN: Prospective, observational study. SETTING: Urogynaecology Unit, NHS Trust hospital. POPULATION: Seventy-seven women undergoing colposuspension. METHODS: Bladder neck elevation was assessed using magnetic resonance imaging and measuring the amount of suture bow-stringing intra-operatively. Urethral compression was assessed using magnetic resonance imaging and by two intra-operative measurements: the distance between the medial sutures (with a ruler) and the distance between the urethra and the pubic bone (using paired Hegar dilators). RESULTS: The assessment of bladder neck elevation and compression against the pubic bone using magnetic resonance imaging was reliable (95% limits of agreement: -7.1mm to +7.1mm and -1.7mm to +3.8mm, correlation coefficient 0.92 and 0.87, respectively). The intra-operative assessment of urethral compression with a ruler was also reproducible at both paravaginal and pectineal sites (95% limits of agreement -2.6mm to +2mm and -2.1mm to +2.4mm, respectively; correlation coefficient 0.99 for both distances). Other intra-operative measurements of bladder neck elevation (suture bow-stringing) and urethral compression (Hegars) did not correlate with equivalent magnetic resonance scan measurements (kappa =-0.046, P = 0.31; kappa = 0.052, P = 0.41, respectively). CONCLUSIONS: Measurements have been found that can reliably assess bladder neck elevation and urethral compression at colposuspension. These measurements should be suitable for investigating morbidity following colposuspension.

Why do women have voiding dysfunction and de novo detrusor instability after colposuspension?

OBJECTIVE: To investigate the causes of voiding dysfunction and new detrusor instability after colposuspension. DESIGN: Prospective, observational study. SETTING: Urogynaecology unit, district general hospital. POPULATION: Seventy-seven women undergoing colposuspension for genuine stress incontinence. METHODS: The following factors were investigated: 1. bladder neck elevation by magnetic resonance imaging before and after surgery; 2. urethral compression by measuring bladder neck approximation to the pubis with magnetic resonance imaging after surgery (anterior compression) and the distance between the medial stitches during surgery (lateral compression); 3. clinical and urodynamic factors. MAIN OUTCOME MEASURES: 1. Post-operative voiding function (i.e. first day of voiding and day of catheter removal); 2. objective evidence of detrusor instability three months post-operatively. RESULTS: Pre-operative peak flow rate (P = 0.004), straining during voiding (P = 0.005), increasing age (P < 0.001), operative elevation (P < 0.001) and anterior urethral compression (P = 0.001) were associated with the number of days of post-operative catheterisation. Increasing age (P = 0.02), previous bladder neck surgery (P = 0.04), operative elevation (P = 0.049) and anterior urethral compression (P < 0.001) were associated with detrusor instability at three months. CONCLUSION: Surgical factors (bladder neck elevation and compression) are associated with voiding dysfunction and detrusor instability after colposuspension. These findings have implications for prevention.

22q13 deletion syndrome.

We have recently collected clinical information on 37 individuals with deletion of 22q13 and compared the features of these individuals with 24 previously reported cases. The features most frequently associated with this deletion are global developmental delay, generalized hypotonia, absent or severely delayed speech, and normal to advanced growth. Minor anomalies include dolicocephaly, abnormal ears, ptosis, dysplastic toenails, and relatively large hands. As with many terminal deletions involving pale G-band regions, the deletion can be extremely subtle and can go undetected on routine cytogenetic analysis. In fact, 32% of the individuals in our study had previous chromosome analyses that failed to detect the deletion. Eight of 37 individuals had deletion of 22q13 secondary to an unbalanced chromosome translocation. In the newborn, this deletion should be considered in cases of hypotonia for which other common causes have been excluded. In the older child, this syndrome should be suspected in individuals with normal growth, profound developmental delay, absent or delayed speech, and minor dysmorphic features. We recommend high-resolution chromosome analysis and fluorescence in situ hybridization studies, or molecular analysis to exclude this diagnosis.

Primitive, crustacean-like state of blood-brain barrier in the eye of the apterygote insect Petrobius (Archaeognatha) determined from uptake of fluorescent tracers.

Compound eyes of insects in 16 orders were tested for the presence of a blood-retina barrier (BRB) by injecting the hemolymph with Procion yellow, which was excluded from the eye in all Neoptera but not in two apterygotes. A primitive apterygote (Petrobius, Machilidae) was investigated further. Epifluorescence observations with small dyes Lucifer yellow (LY) and sulforhodamine 101 (SR) confirmed uptake by the eye within 3 min of injection. LY and SR both penetrated the eye, particularly the cornea, examined in sections. Uptake was quantified by microfluorometry, yielding entry half-times (t(1/2)) of 1-1.4 min, fitting predictions for a model where tracer uptake is limited by passive diffusion. A much larger fluorescent dextran entered at a similar rate (t(1/2) = 1.70 +/- 0.77 min; n = 22), too fast to be diffusion-limited, pointing to an active process, probably flushing of hemolymph through the retina. This is not an artifact associated with tracer injection and may be the natural result of circulatory pressures. Microfluorometry gave a first estimate of hemolymph volume (2.9% of body weight), of hemolymph mixing time (t(0.95) = 77 min); the eyes' receptive fields were also determined. All results point to a primitive crustacean-like condition in Petrobius, with open access of hemolymph to the eye and no BRB. An evolutionary hypothesis is suggested to explain how a primitive central nervous system barrier later extended to cut off the eye in Neoptera, in the face of access problems for respiratory gases and metabolites.

Circadian rhythms in light-evoked responses of the fly's compound eye, and the effects of neuromodulators 5-HT and the peptide PDF.

Two sets of wide-field neurons extend neurites into the fly's optic lamina, where monopolar cells receive photoreceptor input. They exhibit immunoreactivity to antibodies raised against either 5-hydroxytryptamine or the crustacean peptide PDH, respectively. Both are proposed whole-field neuromodulators of vision, apparently regulating a circadian rhythm of monopolar cell size. Seeking functional correlates, we have re-examined the electroretinogram for circadian rhythmicity, and for responses to locally injected 5-hydroxytryptamine and peptide. Long-term electroretinogram recordings from Calliphora entrained to a light/dark cycle and then transferred to constant darkness, uncovered a gradual, modest increase during the subjective night in the electroretinogram's ON- and OFF-transients, from the lamina's monopolar cells. Five to twenty nl of 5-hydroxytryptamine (10(-3) mol.1(-1)) injected into the head haemolymph strongly enhanced the electroretinogram transients, an action reversed by 5-hydroxytryptamine antagonists. Injected into the eye, 5-hydroxytryptamine (10(-4) mol.1(-1)) had the opposite effect; the rapid onset there suggests direct action, whilst the opposing effect from haemolymph injection suggests a different receptor site. Pigment-dispersing hormone (2.2 x 10(-5) mol.1(-1)) injected into the haemolymph increased the electroretinogram transients along a biphasic course, with a slow partial recovery; injected into the eye, it lacked effect.

"Seeking safety": outcome of a new cognitive-behavioral psychotherapy for women with posttraumatic stress disorder and substance dependence.

Women with current posttraumatic stress disorder (PTSD) comprise 30-59% of substance abuse treatment samples and experience a more severe course than women with either disorder alone. As yet, no effective treatment for this population has been identified. This paper reports outcome results on 17 women who completed a new manual-based 24-session cognitive behavioral group therapy protocol treatment, based on assessments at pretreatment, during treatment, posttreatment, and at 3-month follow-up. Results showed significant improvements in substance use, trauma-related symptoms, suicide risk, suicidal thoughts, social adjustment, family functioning, problem solving, depression, cognitions about substance use, and didactic knowledge related to the treatment. Patients' treatment attendance, alliance, and satisfaction were also very strong. Treatment completers were more impaired than dropouts, yet more engaged in the treatment. Overall, our data suggest that women with PTSD and substance abuse can be helped when provided with a treatment designed for them. All results are clearly tentative, however, due to the lack of a control group, multiple comparisons, and absence of assessment of dropouts.

Validity of substance use self-reports in dually diagnosed outpatients.

OBJECTIVE: The purpose of this study was to assess the validity of self-reports of substance use among outpatients dually diagnosed with substance use disorder and either bipolar disorder or posttraumatic stress disorder. METHOD: Self-reports of substance use were compared with supervised urine samples collected on the same day for 55 subjects. RESULTS: Self-reports were highly valid. Only 4.7% of cases involved subjects not reporting substance use detected by urine screens. CONCLUSIONS: Self-reports of substance use may be highly valid in nonpsychotic, dually diagnosed outpatients under certain conditions, i.e., when patients are in treatment, when urine samples are collected with patients' prior knowledge, when patients are well-known to staff, and when honest self-reporting is encouraged.

The link between substance abuse and posttraumatic stress disorder in women. A research review.

Research has documented a high incidence of comorbid post-traumatic stress disorder (PTSD) and substance abuse. Women substance abusers, in particular, show high rates of this dual diagnosis (30% to 59%), most commonly deriving from a history of repetitive childhood physical and/or sexual assault. Rates for men are two to three times lower and typically stem from combat or crime trauma. Patients with both disorders are characterized by high severity on a multitude of psychological and treatment variables and use of the most severe drugs (cocaine and opioids). Treatment research on women is limited but suggests the possibility of retaining patients and achieving positive outcomes.

Re-evaluation of the absolute threshold and response mode of the most sensitive known "vibration" detector, the cockroach's subgenual organ: a cochlea-like displacement threshold and a direct response to sound.

Earlier accounts claim from indirect measurements that the subgenual organ (SGO) in the proximal tibia of the cockroach leg can detect vibrational displacements down to 0.002 nm, two orders of magnitude below the threshold for vertebrate hair cells in the cochlea. The SGO vibration threshold is redetermined here more directly by a new method on a cantilever beam, while controlling for particular acoustic and vibrational artifacts that might have compromised earlier efforts. The threshold is revised upwards to about 0.2 nm in the most sensitive preparation, about the same as the cochlea. Recently, it has been determined that the cockroach SGO also has an auditory response, and the data here on subthreshold summation and response-intensity relationships provide further evidence that sound and contact vibration are both sensed by the same receptor neurons. Direct measurements rule out the prevailing hypothesis that sound is detected indirectly as induced vibration of the ground, and also weigh strongly against any significant involvement of generalized leg resonance in acoustic pick-up. The results fit with a recent proposal that the auditory response is direct, and that acoustic fluctuations inside the tracheae may be the primary response mode in the transduction of both vibration and sound.

Reactive synaptogenesis following degeneration of photoreceptor terminals in the fly's optic lobe: a quantitative electron microscopic study.

Following photo-ablation of receptor cells in the retina of the housefly's compound eye, their synaptic terminals degenerate with a timecourse which we have followed over 8 d. Degeneration deprives the monopolar interneurons in the first optic neuropile, the lamina, of their main synaptic input. Simultaneously it deprives one monopolar interneuron (L2) of one of its synaptic targets, as L2 makes numerous feedback synaptic contacts at which it is pre-synaptic upon receptor terminals. Because the feedback synapses are dyadic, input still remains available to the second element post-synaptic at the dyad, which does not degenerate. This element is T1, a higher-order interneuron from the next most proximal neuropile (the medulla). Some of the original feedback synaptic sites soon disappear as a consequence of the photo-ablation, but their loss is partly offset by the production of new synaptic contacts. The new pre-synaptic ribbons resemble those at the original sites except for being smaller. The sites are, moreover, monadic, with T1 now the sole post-synaptic partner. These results show that interneurons in the fly's lamina retain a dynamic capacity for synaptogenesis throughout much of adult life, normally a few weeks in Musca, and that during this synaptogenesis they re-enact the same cell preferences expressed earlier in development.

PHYLOGENY OF THE SUBFAMILIES OF THE FAMILY BRACONIDAE (HYMENOPTERA: ICHNEUMONOIDEA): A REASSESSMENT.

Abstract- The recently published phylogeny of Braconidae by Quicke and van Achterberg is reassessed. Character-state definitions and character polarities are evaluated, and more rigorous methods are suggested. Our results indicate that there are many more parsimonious solutions to their data set, the consensus of which differs substantially from their results. Based on our reassessment, little can be said about the relationships among braconid subfamilies. Consensus trees show the cyclostomes as a largely unresolved basal grade. The two other major lineages which have been proposed, the helconoids and microgastroids, are somewhat better resolved, but not consistently so. Relationships among the helconoids vary considerably depending on the parameters used for parsimony analysis.

Terminal degeneration and synaptic disassembly following receptor photoablation in the retina of the fly's compound eye.

A long-term objective of our studies on the first optic neuropil (or lamina) underlying the fly's compound eye is to explore how afferent photoreceptor synapses disappear during normal adult experience. To increase the frequency of this loss and the chances for its detection artificially, we have examined in this study the synapses during the degeneration of their presynaptic elements, the synaptic terminals of the receptor cells. This may be reliably procured by illuminating for 12 min with strong green light eyes that have received an injection of the dye sulforhodamine 101 (Picaud et al., 1988). The lesion is local and develops rapidly. Degeneration among terminals is progressive but asynchronous. There are several different types of degeneration, most interpretable as stages in a temporal progression after illumination-induced injury. Degenerative changes include shrinkage and darkening of terminals and mitochondrial swelling. Synaptic sites are lost in a defined sequence: (1) the T-shaped presynaptic ribbon disappears first; (2) the members of what is normally a tetrad of postsynaptic elements withdraw as an ensemble from the receptor terminal's membrane, and the surrounding epithelial glial cells extend between former pre- and postsynaptic partners; and (3) the postsynaptic elements then separate from each other. In the most rapidly affected terminals, the frequencies for those synaptic sites at which both presynaptic ribbons and postsynaptic elements remain intact decline by 85%, even in the first 8 hr postillumination.

Invagination of presynaptic ribbons in the fly's optic lobe following loss of their target neuron.

In the first optic neuropile of the housefly Musca, photoreceptor terminals innervate fixed clusters of interneurons, one of which is the monopolar cell L2; L2's synapses in turn feed back upon the terminals. We examined the ultrastructure of these feedback synapses following degeneration of their normal targets, the receptor terminals; this was accomplished by photo-ablating the receptor cells after intraretinal injections of sulforhodamine. Even when all the terminals degenerated, their deafferentated target cells, including L2, remained structurally intact for at least 14 d. Despite this lack of obvious trans-synaptic degeneration, L2's synaptic connections did alter. Presynaptic organelles of the feedback synapses, synaptic ribbons and associated synaptic vesicles, soon appeared in L2's cytoplasm, separating from their site of attachment at the presynaptic membrane by invagination. Similar free-floating organelles and vesicles also occurred in another monopolar cell, L4. They were also occasionally encountered in L2, in normal, newly emerged flies at a time when a naturally occurring loss of feedback synapses is greatest. We interpret the process of internalization that forms these floating ribbons to be the first step in synaptic loss which occurs spontaneously, and that the rate is enhanced in L2 when its main synaptic targets, the receptor terminals, degenerate.

Changes in geometrical and biomechanical properties of immature male and female rat tibia.

Tibial geometry and mechanical properties in male and female rapidly growing rats were measured to provide comparative data for spaceflight, exercise, or disease experiments that use immature rats as an animal model. A total of 68 immature Sprague-Dawley rats (43-58 d of age) were divided into 8 groups according to age and sex. Tibial length and middiaphysial cross-sectional data were analyzed, and tibial mechanical properties were obtained via three-point bending tests to failure. Results indicated that tibial geometry and mechanical properties were changed significantly during this 15-d period of rapid growth, with male rats having greater increases than female rats. Both male and female tibial lengths nevertheless increased significantly during this growth period, as did middiaphysical cross-sectional area. Tibial flexural rigidity increased significantly for both sexes during this growth period. The male tibiae changed primarily in structural characteristics, but some material properties also changed with age. In the female rats, however, the major changes in mechanical properties of the tibia were attributable only to structural changes in the bone.

Does bupivacaine irrigation of third molar sockets reduce postoperative pain? A double blind controlled trial.

A double blind controlled randomised trial suggested that irrigation of third molar sockets with bupivacaine 0.75% produces significant reduction in pain scored on the first post-operative morning (p less than 0.01). However, this technique produces no significant reduction in opiate or oral analgesic consumption.