Physical health, breastfeeding problems and maternal mood in the early postpartum: a prospective cohort study.

This study aimed to investigate prospectively the contribution of maternal physical health and/or breastfeeding problems to maternal mood (depression, anxiety, fatigue, irritability, confusion, vigor) at 8-weeks postpartum. A prospective study was conducted. Participants were recruited antenatally from a public and a private maternity hospital in Melbourne, Australia. Nulliparous pregnant women (N = 229), ≥ 18 years of age, ≥ 36-week gestation, singleton pregnancy and with sufficient English were eligible. Data were collected by self-report questionnaire (pregnancy, weeks 1-4 postpartum) and telephone interview (week 8 postpartum). A high burden of physical problems was classified as ≥ 3 problems (caesarean/perineal pain; back pain; constipation; haemorrhoids; urinary and bowel incontinence) for ≥ 2 time points. A high burden of breastfeeding problems was having ≥ 2 problems (mastitis; nipple pain; frequent expressing; over- or under-supply of milk) for ≥ 2 time points. Multivariate linear regression was used to investigate the relationship between maternal mood, assessed using Profile of Mood States (8-week postpartum), and a high burden of breastfeeding and/or physical health problems. Forty-six women (20.1%) had a high burden of physical symptoms, 44 (19.2%) a high burden of breastfeeding problems only and 25 women (11.0%) had both. A high burden of breastfeeding problems alone (ß = 10.6, p = 0.01) or with co-morbid physical problems (ß = 15.35, p = 0.002) was significantly associated with poorer maternal mood at 8 weeks. Early, effective postnatal treatment of maternal health and breastfeeding problems could reduce women's risk for poor mental health.

Horse impoundments under Control of Horses legislation in the Munster region of Ireland: factors affecting euthanasia.

Recently, considerable international attention has been paid to the problem of unwanted horses. In Ireland, stray horses, particularly in urban areas, are a further problem. The Control of Horses Act 1996 was enacted in response to an ongoing problem of uncontrolled horses in public places. As yet, no research work has been conducted focusing on stray horses in Ireland. This paper describes horses impounded under the Act in the Munster region of Ireland during 2005-2012 and the factors influencing decisions regarding their disposal. A logistic regression model was developed to investigate factors influencing the probability that a horse was euthanised during impoundment. In total, 3625 seizure events were recorded, most towards the end of the study period. Predictors for euthanasia during 2010-2012 included seizure location, sex, age, colour, body condition score and year. This study highlights the problem of stray horses in Ireland, particularly in urban areas. There is a need for rigorous enforcement of newly enacted horse identification legislation, allowing a fully integrated traceability system. More is required to manage the long-established societal problems of stray horses in urban settings, with a uniform approach by all Local Authorities being long overdue.

Increased common carotid intima-media thickness in UK African Caribbeans and its relation to chronic inflammation and vascular candidate gene polymorphisms.

BACKGROUND AND PURPOSE: Individuals of African Caribbean descent who live in the United Kingdom have an increased risk of stroke. The reasons for this are not fully understood, but differences in genetic predispositions or other novel stroke risk factors could play a role. US blacks have been reported to have increased common carotid artery wall thickness, or intima-media thickness (IMT), measured by ultrasound. We measured carotid IMT in UK African Caribbeans compared with UK whites and determined whether different distributions of polymorphisms in potential candidate vascular genes or differences in measures of chronic inflammation or infection could account for any difference. METHODS: In a population study, common carotid artery IMT was measured in 202 white men and 89 African Caribbean men. The distribution of polymorphisms in ACE, paraoxonase 1, paraoxonase 2, and methylenetetrahydrofolate reductase genes was determined. Serum C-reactive protein and Helicobacter pylori seropositivity were determined. RESULTS: Carotid IMT was increased in African Caribbeans even after controlling for cardiovascular risk factors, including homocysteine and social class: beta=0.113, 95% CI 0.036 to 0.189, P=0.004. There was a significant interaction with smoking and mean IMT (P=0.022), and the difference in both measures of IMT between ethnic groups was largely limited to individuals who had never smoked. There were significant ethnic differences in the distributions of 3 of the 4 candidate genes studied (ACE, paraoxonase 1, and methylenetetrahydrofolate reductase). H pylori seropositivity was increased in African Caribbeans (78.7% versus 53% in UK whites). However, neither the genetic polymorphisms nor H pylori seropositivity was related to IMT, and ethnic differences in their distribution did not account for the increased IMT seen in African Caribbeans. CONCLUSIONS: Carotid IMT is increased in UK African Caribbeans even after controlling for conventional risk factors. There are highly significant ethnic differences in the distribution of many potential cerebrovascular candidate genes. Although those we examined did not explain the ethnic differences in IMT, other genetic predispositions or environmental exposures could account for these differences.

Evaluation of a 1 MHz transducer for transcranial Doppler ultrasound including embolic signal detection.

A 1 MHz transducer for use with transcranial Doppler ultrasound may improve the intensity and therefore the detection of embolic signals (ES) and may also reduce the number of absent acoustic windows. A series of studies was performed to investigate its potential benefits. Firstly, ES were detected using a 1 MHz and a 2 MHz transducer both in vitro and in vivo. Secondly, the time taken to identify 100 middle cerebral arteries (MCA) was recorded for both transducers and the best Doppler signal obtained was reviewed off-line and graded for quality. ES were more intense when detected with the 1 MHz compared with the 2 MHz transducer, both in vitro (p <.0001) and in vivo (p <.0001). Of the 100 MCAs studied, 81 had acoustic windows identified with both transducers. The number of acoustic windows detected with one transducer but not the other was the same for both transducers (n = 3). The time taken to identify the MCA was longer with the 1 MHz transducer (p <.0001) and the quality of the signal achieved was poorer (p <.0001). In conclusion, the 1 MHz transducer improved embolic signal intensity but the overall quality of the flow spectrum obtained was poorer with the 1 MHz than with the 2 MHz transducer. A lower frequency transducer of 1 MHz or possibly 1.5 MHz with transcranial Doppler ultrasound may improve the application of embolic signal detection but may not improve the signal for routine measurement of flow velocities.

Magnetic resonance markers of ischaemia: their correlation with vasodilatory reserve in patients with carotid artery stenosis and occlusion.

OBJECTIVES: Better methods of identifying patients with asymptomatic carotid artery stenosis who are at high risk of stroke are required. It has been suggested that proton magnetic resonance spectroscopy (MRS) may allow the identification of ongoing ischaemia in this patient group by the detection of a potentially reversible reduction of N-acetyl aspartate (NAA), a presumed marker of neuronal integrity, and the presence of lactate, a marker of anaerobic metabolism. Previous studies have reported metabolite ratios rather than absolute concentrations. This study was performed to determine if NAA was reduced ipsilateral to carotid stenosis or occlusion, and if its concentration was related to carbon dioxide reactivity, a marker of cerebrovascular reserve. METHODS: Twenty one patients with unilateral carotid stenosis (>70%) or occlusion were studied. Single voxel proton MRS was performed in the ipsilateral and contralateral hemispheres, with the voxel positioned in the arterial borderzone region between the middle and anterior cerebral artery territories. Absolute quantification of metabolite concentrations was performed. Cerebrovascular reactivity to 6% carbon dioxide was determined in both middle cerebral artery territories using transcranial Doppler ultrasonography. RESULTS: Mean (SD) cerebrovascular reactivity was significantly lower in the stenosed compared with the contralateral hemisphere (13.3 (7.7) v 19.2 (8.2)%/kPa, p=0.002). There were no significant differences in the absolute concentrations of NAA, choline, or creatine between the ipsilateral and contralateral hemispheres (for example, NAA 10.1 (1.1) v 10.5 (1.1) mmol/l, p=0.1). No lactate peak was seen in any spectra. For each metabolite measured, there was no correlation between the absolute concentration and cerebrovascular reactivity for either hemisphere. CONCLUSIONS: In patients with carotid stenosis and occlusion we found no evidence that chronic hypoperfusion is associated with a reduction in NAA or the presence of lactate. Magnetic resonance spectroscopy is unlikely to help in the selection of patients with asymptomatic carotid stenosis for endarterectomy.

C4bp binding to porin mediates stable serum resistance of Neisseria gonorrhoeae.

Screening of 29 strains of Neisseria gonorrhoeae revealed that 16/21 serum resistant strains and 0/8 serum sensitive strains bound C4bp, suggesting that C4bp binding to gonococci could contribute to serum resistance. C4bp bound to gonococci retained cofactor (C4b-degrading) function. Using allelic exchange to construct strains with hybrid Por1A/B molecules, we demonstrate that the N-terminal loop (loop 1) of Por1A is required for C4bp binding. Serum resistant Por1B gonococcal strains also bind C4bp via their Por molecule. Using allelic exchange and site-directed mutagenesis, we have shown that loops 5 and 7 together form a negatively charged C4bp binding domain. C4bp-Por1B interactions are ionic in nature (inhibited by high salt as well as by heparin), while the C4bp-Por1A bond is hydrophobic. mAbs directed against SCR1 of the alpha-chain of C4bp inhibit C4bp binding to both Por1A and Por1B. Furthermore, only recombinant C4bp mutant molecules that contain alpha-chain SCR1 bind both Por1A and Por1B gonococci, confirming that SCR1 contains Por binding sites. C4bp alpha-chain monomers do not bind strains with either Por molecule, suggesting that the polymeric form of C4bp is required for binding to gonococci. Inhibition of C4bp binding to serum resistant Por1A and Por1B strains in a serum bactericidal assay using fAb fragments against C4bp SCR1 results in complete killing at 30 min of otherwise fully serum resistant strains in only 10% normal serum, underscoring the role of C4bp in mediating gonococcal serum resistance.

Severely impaired cerebrovascular reactivity predicts stroke and TIA risk in patients with carotid artery stenosis and occlusion.

Cross-sectional studies suggest that impaired cerebral haemodynamics is associated with symptomatic status in patients with carotid stenosis and occlusion, but there is relatively little prospective data confirming this association. Transcranial Doppler ultrasonography was used to determine the reactivity of the middle cerebral artery to 8% carbon dioxide in air in 107 patients with either carotid occlusion (n = 48) or asymptomatic carotid stenosis (n = 59). Subjects were followed prospectively until stroke, transient ischaemic attack (TIA), death or study end. Mean duration of follow-up was 635 days. No patients dropped out due to operation before an end-point was reached, or were lost to follow-up. There were 11 ipsilateral ischaemic events during follow-up (six strokes, five TIAs). Exhausted ipsilateral middle cerebral artery reactivity (>20% increase in ipsilateral middle cerebral flow velocity in response to 8% carbon dioxide) predicted ipsilateral stroke and TIA risk in the whole group (P: < 0.00001) and in the carotid occlusion (P: = 0.019) and carotid stenosis (P: = 0.015) groups alone. It also predicted the risk of ipsilateral stroke alone in all three groups. Cox regression was performed, controlling for age, gender, hypertension, diabetes, smoking, ipsilateral CT infarct, degree of contralateral stenosis and the presence of ipsilateral stenosis versus occlusion. Exhausted reactivity remained an independent predictor of ipsilateral stroke and TIA (odds ratio 14.4, 95% confidence interval 2.63-78.74, P: = 0.0021). In contrast, the pulsatility index of the middle cerebral artery was a poor predictor of the risk of stroke. Reactivity to 6% carbon dioxide also predicted the risk of stroke and TIA, but slightly less effectively than reactivity to 8% carbon dioxide. Severely reduced cerebrovascular reactivity predicts the risk of ipsilateral stroke and TIA in patients with carotid occlusion, and to a lesser extent in asymptomatic carotid stenosis. Particularly in the former group, a study is required to determine whether revascularization reduces the risk of stroke in patients with exhausted reactivity.

Binding of C4b-binding protein to porin: a molecular mechanism of serum resistance of Neisseria gonorrhoeae.

We screened 29 strains of Neisseria gonorrhoeae and found 16/21 strains that resisted killing by normal human serum and 0/8 serum sensitive strains that bound the complement regulator, C4b-binding protein (C4bp). Microbial surface-bound C4bp demonstrated cofactor activity. We constructed gonococcal strains with hybrid porin (Por) molecules derived from each of the major serogroups (Por1A and Por1B) of N. gonorrhoeae, and showed that the loop 1 of Por1A is required for C4bp binding. Por1B loops 5 and 7 of serum-resistant gonococci together formed a negatively charged C4bp-binding domain. C4bp-Por1B interactions were ionic in nature (inhibited by high salt or by heparin), whereas the C4bp-Por1A bond was hydrophobic. Only recombinant C4bp mutant molecules containing the NH2-terminal alpha-chain short consensus repeat (SCR1) bound to both Por1A and Por1B gonococci, suggesting that SCR1 contained Por binding sites. C4bp alpha-chain monomers did not bind gonococci, indicating that the polymeric form of C4bp was required for binding. Using fAb fragments against C4bp SCR1, C4bp binding to Por1A and Por1B strains was inhibited in a complement-dependent serum bactericidal assay. This resulted in complete killing of these otherwise fully serum resistant strains in only 10% normal serum, underscoring the importance of C4bp in mediating gonococcal serum resistance.

New routes to the United States: special and abbreviated 510(k)s.

Special and Abbreviated 510(k)s are two new approaches to obtaining clearance for medical devices to be marketed in the United States (US) that are designed to streamline the traditional 510(k) review process. This article answers commonly asked questions relating to the requirements for these types of 510(k)s, preparation of applications, and how the US Food and Drug Administration handles these submissions.

Evaluation of new online automated embolic signal detection algorithm, including comparison with panel of international experts.

BACKGROUND AND PURPOSE: The clinical application of Doppler detection of circulating cerebral emboli will depend on a reliable automated system of embolic signal detection; such a system is not currently available. Previous studies have shown that frequency filtering increases the ratio of embolic signal to background signal intensity and that the incorporation of such an approach into an offline automated detection system markedly improved performance. In this study, we evaluated an online version of the system. In a single-center study, we compared its performance with that of a human expert on data from 2 clinical situations, carotid stenosis and the period immediately after carotid endarterectomy. Because the human expert is currently the "gold standard" for embolic signal detection, we also compared the performance of the system with an international panel of human experts in a multicenter study. METHODS: In the single-center evaluation, the performance of the software was tested against that of a human expert on 20 hours of data from 21 patients with carotid stenosis and 18 hours of data from 9 patients that was recorded after carotid endarterectomy. For the multicenter evaluation, a separate 2-hour data set, recorded from 5 patients after carotid endarterectomy, was analyzed by 6 different human experts using the same equipment and by the software. Agreement was assessed by determining the probability of agreement. RESULTS: In the 20 hours of carotid stenosis data, there were 140 embolic signals with an intensity of > or =7 dB. With the software set at a confidence threshold of 60%, a sensitivity of 85.7% and a specificity of 88.9% for detection of embolic signals were obtained. At higher confidence thresholds, a specificity >95% could be obtained, but this was at the expense of a lower sensitivity. In the 18 hours of post-carotid endarterectomy data, there were 411 embolic signals of > or =7-dB intensity. When the same confidence threshold was used, a sensitivity of 95.4% and a specificity of 97.5% were obtained. In the multicenter evaluation, a total of 127 events were recorded as embolic signals by at least 1 center. The total number of embolic signals detected by the 6 different centers was 84, 93, 108, 92, 63, and 78. The software set at a confidence threshold of 60% detected 90 events as embolic signals. The mean probability of agreement, including all human experts and the software, was 0.83, and this was higher than that for 2 human experts and lower than that for 4 human experts. The mean values for the 6 human observers were averaged to give P=0.84, which was similar to that of the software. CONCLUSIONS: By using the frequency specificity of the intensity increase occurring with embolic signals, we have developed an automated detection system with a much improved sensitivity. Its performance was equal to that of some human experts and only slightly below the mean performance of a panel of human experts

Improved automated detection of embolic signals using a novel frequency filtering approach.

BACKGROUND AND PURPOSE: Asymptomatic embolic signal detection with the use of Doppler ultrasound has a number of potential clinical applications. However, its more widespread clinical use is severely limited by the lack of a reliable automated detection system. Design of such a system depends on accurate characterization of the unique features of embolic signals, which allow their differentiation from artifact and background Doppler speckle. We used a processing system with high temporal resolution to describe these features. We then used this information to design a new automated detection system. METHODS: We used a signal processing approach based on multiple overlapping band-pass filters to characterize 100 consecutive embolic signals from patients with carotid artery disease as well as both episodes of artifact resulting from probe tapping and facial movement and episodes of Doppler speckle. We then designed an automated detection system based both on these embolic signal characteristics and on the fact that embolic signals have maximum intensity over a narrow frequency range. This system was tested in real time on stored 5-second segments of data. RESULTS: The value of peak velocity at maximal intensity discriminated best between embolic signals and artifact and allowed differentiation with 100% sensitivity and specificity. Relative intensity increase, intensity volume, area under volume, average rise rate, and average fall rate appeared to discriminate best between embolic signals and Doppler speckle. For the majority of embolic signals, the intensity increase was spread over a narrow frequency or velocity range. The automated system we developed detected 296 of 325 carotid stenosis embolic signals from a new data set (sensitivity, 91.1%). All 200 episodes of artifact from a new data set were differentiated from embolic signals. Only 2 of 100 episodes of speckle were misidentified as embolic signals. CONCLUSIONS: Using a novel system for automated detection, which utilizes the fact that embolic signals have maximum intensity over a narrow frequency range, we have achieved detection with a high sensitivity and high specificity. These results are considerably better than those previously reported. We tested this initial system on short 5-second segments of data played in real time. This approach now needs to be developed for use in a true online system to determine whether it has sufficient sensitivity and specificity for clinical use.

Mapping of cerebrovascular reactivity using BOLD magnetic resonance imaging.

Blood oxygen level-dependent (BOLD) contrast MRI is a simple non-invasive method of estimating "perfusion," and combined with a vasodilatory stimulus, may allow estimation of cerebral vascular reserve. We compared BOLD carbon dioxide (CO2) reactivity in the middle cerebral artery (MCA) perfusion territory to MCA flow velocity reactivity determined using transcranial Doppler ultrasound (TCD) in 16 patients with unilateral carotid artery stenosis or occlusion. Both BOLD and TCD reactivities were calculated from measurements acquired when the subjects were breathing air, and again when breathing a 6% CO2/air mixture, and were normalized by dividing by the difference in end tidal (ET) CO2. There was a significant correlation between interhemispheric MCA reactivity difference (contralateral-ipsilateral to the stenosis or occlusion) determined by BOLD MRI and TCD (r = 0.75, p < 0.001). In contrast, treating each hemisphere individually, there was no correlation between the absolute BOLD and TCD MCA CO2 reactivities (r = 0.08, p = 0.670). This appeared to be due to a variable BOLD signal change in the non-stenosed hemisphere between subjects, with little change in the normal hemisphere of a few subjects. In one patient, focal regions of reduced reactivity were seen in non-infarcted regions of the stenosed hemisphere, in the borderzones between arterial territories. BOLD reactivity maps provide information on the whole MCA territory reactivity, and may identify small regions of impaired reactivity which are not detected using TCD. However, BOLD reactivity maps only appear to provide semi-quantitative rather than quantitative data.

Asymptomatic embolization in subjects with atrial fibrillation not taking anticoagulants: a prospective study.

BACKGROUND AND PURPOSE: Embolism is believed to be the major cause of stroke in patients with nonvalvular atrial fibrillation (NVAF). The detection of asymptomatic embolic signals (ES) in individuals with NVAF might allow identification of patients at high risk of stroke and monitoring of therapy in individual subjects. We determined the frequency of asymptomatic ES in patients with NVAF who were not taking warfarin. METHODS: Bilateral transcranial Doppler recordings were made for 1 hour from the middle cerebral arteries of 111 successive patients with NVAF taking aspirin alone or no antithrombotic or anticoagulant therapy. Adequate recordings could be made in 86 patients. In 79 subjects, recordings were performed on a second occasion to study temporal variability. Recordings for a single hour were also made in 30 age-matched control subjects. RESULTS: ES were detected in 13 (15.1%) of NVAF subjects but in no control subjects (P=0.02). ES were detected both in subjects with symptomatic NVAF (4 of 30 [13.1%], P=0.04 versus controls) and asymptomatic NVAF (9 of 56 [16.1%], P=0.02 versus controls). There was no correlation between the presence of ES and smoking status, diabetes, hypertension, aspirin use, aspirin dose, symptomatic status, left atrial size, left ventricular function, or the presence of left atrial thrombus detected on transthoracic echocardiography. Repeating the recording increased the number of patients with ES to 21 (26.6%). On considering the results of both recordings, again there was no association for either recording between the presence of ES and smoking status, diabetes, hypertension, aspirin use, aspirin dose, age, symptomatic status, left atrial size, or left ventricular function. On repeating the recording, in the symptomatic group only 2 patients (8%) changed status, in contrast to 15 (29%) in the asymptomatic group. CONCLUSIONS: ES can be detected in patients with NVAF at a low frequency. Particularly in asymptomatic patients, ES show marked temporal variability. We found no correlation between the presence of previously reported clinical and echocardiographic markers of increased stroke risk and the presence of ES. This association requires further investigation before the clinical utility of this technique in patients with NVAF is decided.

Pathogenetic considerations of pica in lead poisoning.

An important factor associated with lead poisoning in children is the habit of eating non-food substances, a condition termed pica. In search for underlying mechanisms involved in the pathogenesis of pica, this investigation presents evidence in support of the hypothesis that in many families failure of normal mother-child interaction, paternal deprivation, culturally dependent maternal oral interests and significant stress factors in the home where abundant lead-containing material is available are etiologically related to the development of pica in lead poisoning. Other factors, which have been thought to be associated with pica, are nutritional deficiencies and maladaptive behavior patterns. A multifocal treatment approach is considered to be most effective.