Antepartum risk factors for newborn encephalopathy. Intrapartum risk factors are important in developing world.
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Biomedical subjects
Publications and source records attributed to M Ellis.
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The Kaposi's sarcoma-associated human herpesvirus 8 (KSHV/HHV8) encodes a protein similar to cellular cyclins. This cyclin is most closely related to cellular D-type cyclins, but biochemically it behaves atypically in various respects. Complexes formed between the viral cyclin and the cyclin-dependent kinase subunit, cdk6, can phosphorylate a wider range of substrates and are resistant to cdk inhibitory proteins. We show here that the KSHV-cyclin-cdk6 complex phosphorylates p27(Kip) on a C-terminal threonine that is implicated in destabilization of this cdk inhibitor. Expression of the viral cyclin in tissue culture cells overcomes a cell cycle block by p27(Kip). However, full cell-cycle transit of these cells appears to depend on C-terminal phosphorylation of p27(Kip) and seems to involve transactivation of other cellular cyclin-dependent kinases. A p27(Kip)-phosphorylating cdk6 complex exists in cell lines derived from primary effusion lymphoma and in Kaposi's sarcoma, this indicating that virally induced p27(Kip) degradation may occur in KSHV-associated tumours.
BACKGROUND: Falls in elderly people are a common presenting complaint to accident and emergency departments. Current practice commonly focuses on the injury, with little systematic assessment of the underlying cause, functional consequences, and possibilities for future prevention. We undertook a randomised controlled study to assess the benefit of a structured inderdisciplinary assessment of people who have fallen in terms of further falls. METHODS: Eligible patients were aged 65 years and older, lived in the community, and presented to an accident and emergency department with a fall. Patients assigned to the intervention group (n=184) underwent a detailed medical and occupational-therapy assessment with referral to relevant services if indicated; those assigned to the control group (n=213) received usual care only. The analyses were by intention to treat. Follow-up data were collected every 4 months for 1 year. FINDINGS: At 12-month follow-up, 77% of both groups remained in the study. The total reported number of falls during this period was 183 in the intervention group compared with 510 in the control group (p=0.0002). The risk of falling was significantly reduced in the intervention group (odds ratio 0.39 [95% CI 0.23-0.66]) as was the risk of recurrent falls (0.33 [0.16-0.68]). In addition, the odds of admission to hospital were lower in the intervention group (0.61 [0.35-1.05]) whereas the decline in Barthel score with time was greater in the control group (p<0.00001). INTERPRETATION: The study shows that an interdisciplinary approach to this high-risk population can significantly decrease the risk of further falls and limit functional impairment.
BACKGROUND: Mycobacterium tuberculosis of the cervical spine is a rare but dangerous manifestation of extra-pulmonary tuberculosis. The clinical picture ranges from early, nonspecific, insidious symptoms to severe neurological complications and death, attributed to craniocervical junction instability and cervicomedullary compression. The different lines of management include antituberculous medication with traction and external fixation or adjunctive surgery (debridement and stabilization) in patients with severe or persistent neurological complications and/or vertebral instability. METHODS: We describe two patients with advanced craniocervical junction tuberculosis. The early clinical picture was nonspecific in Case 1 and obscured by psychiatric illness in Case 2. The detailed clinical and radiological findings, and the management, will be described. Involvement of the occipital condyles and foramen magnum, which has not been reported previously, will be demonstrated. RESULTS: Both cases underwent transoral biopsy, aspiration, and debridement of retropharyngeal abscess (granuloma). Histological and tissue culture studies proved the abscesses were tuberculous and anti-tuberculous medications were started. Case 1 showed complete resolution of the clinical and radiological findings. Case 2 developed cardiorespiratory arrest while in a halo jacket. He was resuscitated but remained quadriplegic and semiconscious; he developed nosocomial gram negative pneumonia. He was referred back to his local hospital where he died 1 year later. CONCLUSIONS: Tuberculosis is an infrequent but notable cause of cervicomedullary compression. It should be suspected in patients with infective spondylitis who are immunocompromised or reside in an area highly endemic for tuberculosis. Management strategies include antituberculosis medication, transoral biopsy and drainage of the abscess, traction and external fixation, posterior decompression, and internal fixation, according to the clinical and radiological findings.
OBJECTIVE: The aim of this study was the definition of the duplex scan parameters that best select patients for carotid endarterectomy. METHODS: This study was set in a regional vascular unit. Duplex scanning and angiography were performed prospectively on 50 patients who were symptomatic (100 carotid bifurcation) to identify the most accurate and sensitive duplex scan criteria to identify an 80% to 99% stenosis according to the European Carotid Symptomatic Trial. With data from the European Carotid Symptomatic Trial, we estimated the effect of three different approaches used to select patients for carotid endarterectomy. The first approach was the selection of patients for carotid surgery on the basis of duplex scanning alone with the most accurate duplex scan criteria (approach I). The second approach was the selection of patients for carotid surgery on the basis of duplex scanning alone with a 100% sensitive duplex scan criteria (approach II). The third approach was the selection of patients for angiography with duplex scanning (100% sensitive criteria) and then the use of angiography to define which patients should undergo surgery (approach III). RESULTS: All three approaches appeared to have a similar potential in stroke reduction. However, approach I, which minimized the number of patients who underwent surgery (19% less than approach II) or invasive imaging (65% less than approach III), appeared to be the most appropriate. CONCLUSION: These data support the selection of patients for carotid endarterectomy on the basis of duplex scanning alone. The duplex scan criteria should be validated against angiography.
To determine the outcome at 1 year of neonatal encephalopathy (NE) and to estimate the possible contribution of birth asphyxia to childhood disability in a low-income South Asian country, a prospective cohort study was undertaken in the principal maternity hospital of Kathmandu, where over 50% of local women give birth. From a total population cohort of 21609 live births, 131 term infants with NE (after exclusion of cases associated with neonatal sepsis, congenital malformations, or primary hypoglycaemia) and 208 term control infants were recruited. Of these, 102 (78%) infants with NE and 106 (51%) control infants were followed-up to 1 year of age. Outcome measures were death or neurodevelopmental impairment, graded as major, minor or none. Of the 131 term infants with NE, 83 were graded with moderate or severe NE according to conventional definition. By 1 year of age, 45 (44%) of the infants with NE had died, 18 (18%) had severe impairments, and two (2%) had minor impairments; four (4%) of the control subjects had died and two (2%) had minor impairments. Most deaths in subjects with NE occurred in the early neonatal period; NE carried no excess risk of death beyond the neonatal period. Of the 18 children with major impairment, 14 (78%) had spastic tetraplegic cerebral palsy and eight (44%) had multiple impairments. Compared with the control group the relative risk of death by 1 year was 5 (95% CI 1.4 to 15) for mild NE, 8 (95% CI 3 to 23) for moderate, and 26 (95% CI 10 to 67) for severe. Twenty-seven of 38 (71%) infants with moderate NE either died or survived with major impairment. An upper estimate for the prevalence of major neuroimpairment at 1 year attributable to birth asphyxia is 1 per 1000 live births in this population.
There has been growing consensus that children with conduct disorder (CD) constitute a very heterogeneous group containing children who vary substantially on the development, course, and causes of the disorder. While many have recognized the importance of this heterogeneity for developing better causal theories and for developing more effective treatments, there has been little consensus as to the best way to subtype children with CD. In this paper, we review a number of approaches to subtyping, each with some evidence for its validity for certain purposes. We focus on two recent approaches that have great potential for integrating past subtyping approaches and for advancing causal theory. The first approach is the division of children with CD into those with a childhood onset to their severe antisocial behavior and those with an adolescent onset to their behavior. The second approach is to designate children within the childhood-onset group who show callous and unemotional traits, which is analogous to adult conceptualizations of psychopathy. Both approaches help designate children who many show different causal processes underlying their severe aggressive and antisocial behavior, and who may warrant different approaches to treatment.
Although several theoretical models posit that low levels of anxiety are a risk factor for psychopathy and antisocial behavior, a number of studies have reported elevated levels of anxiety among antisocial individuals. Nevertheless, most investigators in this literature have not distinguished between fearfulness and trait anxiety or attempted to separate the antisocial lifestyle dimension from the callous and unemotional dimension of psychopathy. In a study of clinically referred children (N = 143), we found that (a) measures of trait anxiety and fearlessness (low fearfulness) exhibited low correlations; (b) conduct problems tended to be positively correlated with trait anxiety, whereas callous and unemotional traits tended to be negatively correlated with trait anxiety; and (c) controlling statistically for the effects of one dimension increased the divergent correlations of the other dimension with both trait anxiety and fearful inhibition. These findings bear potentially important implications for the diagnosis and etiology of psychopathy and antisocial behavior and suggest that distinctions between trait anxiety and fearful inhibition, as well as between the two dimensions of psychopathy, may help to clarify longstanding confusion in this literature.
UNLABELLED: Both acute normovolemic hemodilution (NVHD) and tranexamic acid (TA) are potentially useful allogeneic blood conservation strategies after total knee replacement. However, the relative efficacy of these blood-sparing techniques is unknown. Therefore, to compare the postoperative allogeneic blood sparing of NVHD and TA after total knee replacement, we investigated 40 patients in a prospective, single-blinded study protocol. In Group TA, 30 min before deflating the limb tourniquet, an IV infusion of TA, 15 mg/kg, was administered over a 30-min period. Thereafter, a constant IV infusion of 10 mg x kg(-1) x hr(-1) was administered until 12 h after deflation of the limb tourniquet. Before induction of anesthesia, NVHD patients were bled to a target hematocrit of approximately 28%. Intravascular blood volume was maintained with lactated Ringer's solution. All autologous blood was transfused at the end of the surgery. Postoperatively, hematocrit was measured daily. In all cases, a hematocrit <27% was the postoperative transfusion trigger. Before discharge, deep vein thrombosis was excluded by Echo Doppler. Three months after surgery, the incidence of delayed thromboembolic events was assessed. The two groups were demographically comparable. In Group NVHD, 843 mL+/-289 of autologous blood was removed. Despite autologous blood transfusion, during the early postoperative period and until the third postoperative day, the NVHD group had significantly (P < 0.01) lower mean hematocrits when compared with the TA group. Thereafter, because of a significantly (P < 0.0008) greater allogeneic blood requirement in the NVHD group, no statistically significant difference in mean hematocrit recordings was noted among the groups. Blood accumulation in the surgical drain 12 h postoperatively, was significantly (P < 0.0008) higher in the NVHD group (259 mL+/-156) when compared with the TA group (110 mL+/-62). Significantly (P < 0.0008) more allogeneic blood was transfused in the NVHD group (19 U/13 patients) when compared with the TA group (2 U/2 patients). No abnormal Echo Doppler studies were reported. During the 3-mo follow-up period, a deep vein thrombosis and pulmonary embolus were documented in one patient in the NVHD group. We conclude that perioperative hemodynamic stability and allogeneic blood sparing is superior after tranexamic acid administration when compared with normovolemic hemodilution. IMPLICATIONS: For total knee replacement, when compared with normovolemic hemodilution, tranexamic acid administration is associated with superior perioperative hemodynamic stability and allogeneic blood sparing.
OBJECTIVE: To assess prospectively the outcome of femoropopliteal angioplasty and investigate prognostic indicators of success. BACKGROUND: Percutaneous transluminal angioplasty is commonly used to treat symptomatic femoropopliteal stenoses or occlusions, but the durability of the procedure is uncertain. METHODS: Seventy-four consecutive patients treated by femoropopliteal angioplasty for intermittent claudication (43), rest pain (4), and tissue loss (27) were followed by assessment of symptoms, ankle-brachial pressure index (ABPI) to measure hemodynamic outcome, and duplex monitoring of velocity gradient at the angioplasty site to identify restenosis at 1 day and 3, 6, 9, and 12 months. Univariate comparisons, life table analysis, and backward stepwise regression were used to investigate factors predicting the symptomatic and hemodynamic outcome and restenosis. RESULTS: Technical success was obtained in 67 patients (91%); failure occurred in 7 patients. At 1 year, a successful symptomatic outcome was achieved in 35 patients (51%), hemodynamic success was achieved in 41 patients (58%), and restenosis developed in 39%. ABPI at 24 hours after angioplasty was the most significant variable predicting a symptomatic outcome, hemodynamic outcome, and restenosis at 12 months. Life table analysis demonstrated that in 24% of patients with a 24-hour ABPI > or =0.9, restenosis developed by 12 months, compared with 64% of patients with a 24-hour ABPI <0.9. CONCLUSION: Only half of the patients treated by femoropopliteal angioplasty had symptomatic improvement at 1 year, raising concern about the cost-benefit ratio of this procedure. Restoration of ABPI to >0.9 predicted a favorable outcome.
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Mixed-parity sows (n = 267) from five research stations were used to investigate whether a reduction of excess dietary amino acids would improve feed intake and performance of lactating sows experiencing heat stress. Experimental treatments included effects of room temperature (warm or hot) and diet (adequate protein [AP] or low protein [LP]). The corn-soybean meal AP diet was formulated to contain 16.5% CP, .8% lysine, and .67% digestible lysine. The LP diet was formulated to contain 13.7% CP, .76% lysine, and .66% digestible lysine using corn, soybean meal, and synthetic lysine. Feed intake during gestation was standardized at 1.8 kg x sow(-1) x d(-1). At parturition, litter size was adjusted to no fewer than nine pigs. Mean high temperature in the warm and hot rooms was 20.4 and 29.2 degrees C and mean low temperature was 17.7 and 27.1 degrees C, respectively. The hot environment reduced (P < .01) feed intake of sows (4.19 vs 6.38 kg/d) during lactation, weaning weight of sows (176.2 vs 193.6 kg), percentage of sows displaying estrus (79.2 vs 93.4%) by d 15 postweaning, and litter growth rate (1.74 vs 2.11 kg/d) and increased (P < .01) respiration rate of sows on d 10 postpartum (71.9 vs 36.5 breaths/min) compared with the warm environment. Litter size and backfat loss of sows were not affected by treatments. No significant diet x room temperature interactions were observed for voluntary feed intake, body weight loss, backfat loss, or respiration rate of sows. Litter growth rate was depressed by feeding the LP diet in the warm room but was improved by feeding the LP diet in the hot room (warm-AP, 2.17; warm-LP, 2.05; hot-AP, 1.71; hot-LP, 1.77 kg/d; P < .05). Reduction of dietary crude protein combined with supplementation of crystalline lysine to reduce concentrations of excess dietary amino acids did not significantly reduce heat stress of sows, but it did support slight improvements in weight gain of litters nursing heat-stressed sows.
The DNA-binding properties of a series of 2-aza-anthracenedione (benz[g]isoquinoline-5,10-dione) derivatives bearing two 3-dimethylaminopropylamino side chains at different (6,9, 7,9 and 8,9) positions of the planar ring system have been investigated. The affinity for the nucleic acid is dramatically affected by the substitution pattern, the 6,9-regioisomer being substantially more effective than the 7,9- or the 8,9-congeners. This cannot be ascribed to different binding mechanisms, as all compounds are shown to intercalate into the double helix. Instead, the geometry of intercalation into DNA and the site specificity are extensively affected by the substitution pattern. The site preference is CA (or AC) for the 6,9-regioisomer, whereas it is TA (or AT) for the 8,9-congener, the 7,9-analogue lying in between. Molecular modeling studies are in agreement with the experimental results. Although the 6,9-regioisomer was remarkably cytotoxic, it stimulated topoisomerase II-mediated cleavage of DNA very poorly. Hence, a different mechanism of DNA damage is probably operating in 2-aza-anthracenediones as the main cell-killing event. Changes in affinity for DNA, intercalation geometry and sequence specificity can explain the different cytotoxic responses exhibited by the test drugs.
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Progression of cells into S phase is controlled by the retinoblastoma protein (pRB) and relies on the functional inactivation of this tumour suppressor in late G1 via protein phosphorylation. We provide evidence here that, besides controlling entry of cells into S phase, pRB can operate to inhibit S phase completion. Differential arrays of phosphorylation appear to regulate these different events, suggesting that cycle progression at these two stages of the cell cycle may be achieved via activation of distinct downstream pRB effector pathways. In agreement with this hypothesis, pRB's ability to prevent S phase entry, but not its ability to inhibit S phase completion, correlates with repression of E2F-regulated promoters. Furthermore, ectopic expression of E2F or the E2F-regulated cyclin E gene promote S phase entry in cells expressing phosphorylation-defective pRB but neither is sufficient to trigger completion of S phase. Our findings raise the possibility that pRB, in addition to its well-established role in controlling a checkpoint in late G1, could be involved in the control of a further checkpoint operating during S phase and that implementation of this checkpoint relies on an as yet unidentified pRB effector distinct from E2F.
OBJECTIVES: To evaluate impact of postnatal health education for mothers on infant care and postnatal family planning practices in Nepal. DESIGN: Randomised controlled trial with community follow up at 3 and 6 months post partum by interview. Initial household survey of study areas to identify all pregnant women to facilitate follow up. SETTING: Main maternity hospital in Kathmandu, Nepal. Follow up in urban Kathmandu and a periurban area southwest of the city. SUBJECTS: 540 mothers randomly allocated to one of four groups: health education immediately after birth and three months later (group A), at birth only (group B), at three months only (group C), or none (group D). INTERVENTIONS: Structured baseline household questionnaire; 20 minute, one to one health education at birth and three months later. MAIN OUTCOME MEASURES: Duration of exclusive breast feeding, appropriate immunisation of infant, knowledge of oral rehydration solution and need to continue breast feeding in diarrhoea, knowledge of infant signs suggesting pneumonia, uptake of postnatal family planning. RESULTS: Mothers in groups A and B (received health education at birth) were slightly more likely to use contraception at six months after birth compared with mothers in groups C and D (no health education at birth) (odds ratio 1.62, 95% confidence interval 1.06 to 2.5). There were no other significant differences between groups with regards to infant feeding, infant care, or immunisation. CONCLUSIONS: Our findings suggest that the recommended practice of individual health education for postnatal mothers in poor communities has no impact on infant feeding, care, or immunisation, although uptake of family planning may be slightly enhanced.
Space geodetic data recorded rates and directions of motion across the convergent boundary zone between the oceanic Nazca and continental South American plates in Peru and Bolivia. Roughly half of the overall convergence, about 30 to 40 millimeters per year, accumulated on the locked plate interface and can be released in future earthquakes. About 10 to 15 millimeters per year of crustal shortening occurred inland at the sub-Andean foreland fold and thrust belt, indicating that the Andes are continuing to build. Little (5 to 10 millimeters per year) along-trench motion of coastal forearc slivers was observed, despite the oblique convergence.