Mutations in the factor XI gene.
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Codon, Nonsense↗
Biomedical subjects
M Smith
Publications and source records attributed to M Smith.
Morbidity and mortality in rheumatoid arthritis patients with prolonged and profound therapy-induced lymphopenia.
OBJECTIVE: Therapies that deplete lymphocytes often improve symptoms in patients with otherwise refractory autoimmune disease but may result in long-term lymphopenia, the consequences of which are uncertain. To assess the impact of prolonged lymphopenia on morbidity and mortality, we studied patients who had previously received lymphocytotoxic monoclonal antibody (mAb) therapy for rheumatoid arthritis (RA). METHODS: Fifty-three patients who received the lymphocytotoxic mAb CAMPATH-1H between 1991 and 1994 in the United Kingdom were assessed for mortality and infectious and malignant morbidity, by interview and case-note review. In addition, patients were monitored via the National Health Service Central Registry, to verify notification of death. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. A retrospective, matched-cohort study of mortality was also performed with 102 control subjects selected from the European League Against Rheumatism database, which comprises patients with rheumatic disorders who have received immunosuppressive drugs. RESULTS: There was profound and persistent peripheral blood lymphopenia in the mAb-treated patients, affecting predominantly the CD4+ subset. Median CD4+, CD8+, and CD19+ peripheral blood lymphocyte counts at 73-84 months after therapy were 185 cells/microl, 95 cells/microl, and 115 cells/microl, respectively. At a median followup of 71 months (range 14-90), 13 patients had died (24.5%), compared with 18% of the matched controls, providing a mortality rate ratio of 1.45 (95% confidence interval 0.65-3.13). During 283 patient-years of followup, there were 36 infections classified as major (12.7 per 100 patient-years). The causes of death and the spectrum of infections documented were similar to those expected in a hospital-based RA cohort. Patients who received more than 1 course of therapy had more severe lymphopenia than did patients who received a single course, but this did not have an impact on mortality or morbidity. CONCLUSION: Despite the occurrence of profound and long-lasting lymphopenia following treatment with antilymphocyte mAb therapy for RA, this therapy is not associated with a large excess of mortality nor with an unusual spectrum of infections, at least during a medium-term period of followup. These data are also relevant to patients receiving lymphocytotoxic mAb therapy for other indications, and to patients receiving other lymphodepleting therapies such as autologous stem cell transplantation.
Aged↗
Fully automatic anatomical, pathological, and functional segmentation from CT scans for hepatic surgery.
OBJECTIVE: To improve the planning of hepatic surgery, we have developed a fully automatic anatomical, pathological, and functional segmentation of the liver derived from a spiral CT scan. MATERIALS AND METHODS: From a 2 mm-thick enhanced spiral CT scan, the first stage automatically delineates skin, bones, lungs, kidneys, and spleen by combining the use of thresholding, mathematical morphology, and distance maps. Next, a reference 3D model is immersed in the image and automatically deformed to the liver contours. Then an automatic Gaussian fitting on the imaging histogram estimates the intensities of parenchyma, vessels, and lesions. This first result is next improved through an original topological and geometrical analysis, providing an automatic delineation of lesions and veins. Finally, a topological and geometrical analysis based on medical knowledge provides hepatic functional information that is invisible in medical imaging: portal vein labeling and hepatic anatomical segmentation according to the Couinaud classification. RESULTS: Clinical validation performed on more than 30 patients shows that delineation of anatomical structures by this method is often more sensitive and more specific than manual delineation by a radiologist. CONCLUSION: This study describes the methodology used to create the automatic segmentation of the liver with delineation of important anatomical, pathological, and functional structures from a routine CT scan. Using the methods proposed in this study, we have confirmed the accuracy and utility of the creation of a 3D liver model compared with the conventional reading of the CT scan by a radiologist. This work may allow improved preoperative planning of hepatic surgery by more precisely delineating liver pathology and its relationship to normal hepatic structures. In the future, this data may be integrated with computer-assisted surgery and thus represents a first step towards the development of an augmented-reality surgical system.
Humans↗
The recovery of walking ability and subclassification of stroke.
BACKGROUND AND PURPOSE: The recovery of walking after a stroke is a key functional goal for many patients. Reports vary, but approximately 50-80% of patients will regain some degree of walking ability following stroke (Skilbeck et al., 1983). There are few data available to show whether different subclassifications of stroke have distinct patterns of gait recovery. The present paper describes the pattern of walking recovery in a population of stroke patients classified according to the Oxfordshire Community Stroke Project classification (Bamford et al., 1991). METHOD: A prospective observational study. Stroke patients (n = 238) admitted to the inpatient Stroke Rehabilitation Unit at the Western General Hospital, Edinburgh were initially included, with data for 185 patients ultimately available for analysis. Standardized measures of recovery of 10 steps and a 10-metre walk were used routinely to examine recovery time of walking ability. The main outcome measures consisted of days taken to achieve a 10-step walk, days to achieve a 10-metre walk, and initial and discharge gait velocity over 10 meters. RESULTS: Eighty-nine per cent of the sample (n = 164) achieved a 10-step walk in a median time of five days and a 10-metre walk in eight days. The median initial gait velocity was 0.45 m/s which improved by discharge to 0.55 m/s. Further analysis by subgroup revealed that subjects sustaining a partial anterior circulation infarct, lacunar infarct or posterior circulation infarct recovered significantly more quickly than those subjects with a total anterior circulation infarct (Kruskal Wallis test for days to achieve 10 steps (H = 22.524, N = 164, df = 3) p < 0.001; Kruskal Wallis test for days to achieve a 10-metre walk (H = 22.586, N = 164, df = 3) p < 0.001. CONCLUSIONS: An hierarchical pattern of recovery of gait was observed with definite variation between the subclassifications of stroke. It is suggested that further work needs to be undertaken to identify more accurately the factors that may influence the recovery of walking following stroke.
Age Factors↗
Manometric squeeze pressure difference parallels functional outcome after overlapping sphincter reconstruction.
PURPOSE: This study was designed to evaluate the effectiveness of overlapping anal sphincter reconstruction and to determine the manometric parameters that correlate with a successful functional outcome. METHODS: A retrospective review of patients who had undergone overlapping sphincter reconstruction for anal incontinence from 1988 to 1999 was undertaken. Only patients with preoperative and six-months-postoperative anal manometry were included in this study. Standard statistical tests were used to compare pre- and postoperative findings. RESULTS: A total of 52 overlapping sphincter reconstructions were performed on 49 patients (46 females). The mean age was 44 (+/- standard error, 15.8; range, 20-81) years, with follow-up at six months. Forty-two patients had a history of complicated vaginal delivery (episiotomies, tears, forceps delivery); 36 patients had a history of anal or perineal surgery; and two patients had perianal Crohn's disease. Nine patients (17 percent) had undergone prior sphincter repair. Incontinence grade improved in 37 patients (71 percent), and complete continence returned in 21 patients (40 percent). The presence of a rectovaginal fistula, postoperative complications, previous sphincter repair, and increase in pudendal nerve terminal motor latency did not affect functional outcome (P = not significant). Patients older than 50 years had a better functional outcome than their younger counterparts after sphincter repair (P = 0.02). Although mean maximal squeeze pressure and mean anal sphincter length increased significantly after sphincter reconstruction (P = 0.0006 and 0.004, respectively), only squeeze pressure difference correlated with functional outcome (r = 0.37; P = 0.007). CONCLUSIONS: Overlapping sphincter reconstruction improved anal function in the majority of patients. The most important factor in the return to normal sphincter function is an increase in squeeze pressure.
Adult↗
Teleeducation in surgery: European Institute for Telesurgery experience.
The information age is revolutionizing the practice and education of surgery. The use of video-conference systems through Integrated Service Digital Network (ISDN) teletransmission connects surgeons around the world without the limits of distance. Teleeducation, teleteaching, teletraining, telementoring, and teleaccreditation have been clearly demonstrated and are now common practice. Pre- and perioperative surgical advice may be obtained from expert networks. Patient data can be reconstructed as virtual tridimensional images analyzed by computers, and the surgical procedure can be simulated to obtain an optimal surgical decision. Finally, the use of the Internet will provide access to this information, whenever and wherever necessary, through dedicated websites. It remains to be adequately demonstrated that these means will allow improvement in patient care.
Computer Simulation↗
Syntactic priming in spoken sentence production - an online study.
Six experiments investigate syntactic priming online via a picture description task in which participants produce target sentences whose initial phrase is syntactically similar or dissimilar to that of the prime sentence produced on the previous trial. In the first experiment it is shown that a syntactically related prime sentence speeds onset latencies to a subsequent target sentence by approximately 50 ms relative to a syntactically unrelated prime sentence. In the second experiment, the cost of the process of lemma access is factored out via a picture previewing technique but a priming effect is still obtained demonstrating that the effect is not a product of the priming of lemma access processes. In Experiment 3, the related and unrelated prime trials feature the same picture display but the 50 ms facilitation effect is still observed indicating that the effect does not result from the priming of visual perception of the picture movements. This is further strengthened in Experiment 4 which uses written prime sentences rather than a picture description task on the prime trial and still obtains a facilitation effect. In Experiment 5, the effect disappears when the participants are instructed to name the movements but not the objects depicted in the array and this is interpreted as evidence against the view that the effect results from the conceptualization of the events depicted by the array. In the final experiment, the scope of the syntactic persistence effect is investigated by priming sentences with initial phrases of varying syntactic complexity. Significant priming is only observed for an initial phrase featuring two nouns - a finding consistent with the view that the syntactic persistence effect applies only to the generation of the first phrase of an utterance prior to speech onset. The implications of these results are analyzed in the final discussion section.
Adult↗
Development of the phytoplankton community in a pit-lake in relation to water quality changes.
An open pit-lake was formed at a Northern Saskatchewan mine site after flooding with lake water in early 1992. Since then, water and phytoplankton samples have been collected regularly from the artificial lake over seven years. The resulting data set provides a unique opportunity to examine the physical and chemical changes in water quality and phytoplankton community over time. Seventeen major variables were examined in a principal component analysis. Axes 1, 2 and 4 are significantly correlated to other three variables, the number of days (since the first sampling after flooding of the pit), water temperature and depth, respectively. Total suspended solid (TSS), dissolved oxygen, total phosphorus (Total-P), arsenic, and iron decreased over time while Mg, Ca, K, Na, total organic carbon and HCO3 increased. Canonical correspondence analysis was used to infer the relationship between water quality variables and phytoplankton community structure, which changed substantially over the survey period. TSS, Total-P and arsenic were considered to be the key factors driving the change in phytoplankton community composition.
Canada↗
Indirect allorecognition and alloantibody production precede obliterative airway disease development after tracheal transplantation in mice.
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Journal Article↗
Guillain-Barre syndrome: a patient's experience.
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Adolescent↗
Expression of the FAE1 gene and FAE1 promoter activity in developing seeds of Arabidopsis thaliana.
Plant fatty acid elongase which catalyzes very-long-chain fatty acid (VLCFA) biosynthesis is a membrane-bound multienzyme complex. It is composed of four enzymes, a 3-ketoacyl-CoA synthase (condensing enzyme), a 3-ketoacyl-CoA reductase, a 3-hydroxyacyl-CoA dehydrase, and an enoyl-CoA reductase required for completion of each step of 2-carbon elongation of fatty acids. To improve our understanding of the overall regulation of the fatty acid elongase, we investigated the spatial and temporal expression of its key component, the FAE1-condensing enzyme, and examined the activity of the promoter of the FAE1 gene in Arabidopsis. In situ hybridization results revealed that FAE1 transcripts were found exclusively in the embryo. RNA blot analysis and histochemical analysis of GUS activity in pFAE1::GUS transgenic Arabidopsis lines demonstrated that the FAE1 gene was already transcribed in the early torpedo stage embryos 4-5 days after flowering, with transcription reaching its peak 9-11 days after flowering. VLCFA deposition closely paralleled FAE1 transcript accumulation. FAE1 promoter was highly active and embryo-specific. Because its timing coincides with the period of major storage lipid accumulation, and because its in vivo activity in Arabidopsis is superior to the napin promoter, FAE1 promoter may be ideal for genetic engineering of seed oil composition.
Acetyltransferases↗
Polymorphic CA repeats in the IGF-I gene and breast cancer.
Insulin-like growth factor (IGF)-I is a potent mitogen for breast cancer cells and may play a role in the disease. Although the involvement of IGF-I phenotype in breast cancer has been studied extensively, little is known about IGF-I genotype in relation to the disease. The IGF-I gene contains a polymorphic region composed of multiple cytosine-adenine dinucleotides (CA repeats). Studies of other genes indicate that the CA-repeat region in the promoter of a gene may affect transcription activity and that the length of the repeat is inversely correlated with transactivation. To examine if the IGF-I polymorphism is associated with breast cancer, we compared the length of CA repeats in the IGF-I gene between 53 breast cancer patients and 53 controls. Genomic DNA extracted from peripheral blood was used to determine the number of CA repeats through PCR amplification and DNA sequencing. Associations between CA repeats and breast cancer were assessed using unconditional logistic regression analysis. The results showed that the median number of CA repeats was 19, ranging from 15 to 23, and that compared to women without 19 CA repeats, women with 19 CA repeats were more likely to be breast cancer patients (OR = 2.87, 95%CI: 1.16-7.06) after adjusting for age, race, menopausal status, age at menopause, and alcohol use. The study also suggested possible synergistic interplay between IGF-I genotype and phenotype as women with 19 CA repeats and high plasma IGF-I had a much higher odds ratio for breast cancer (OR = 5.12, 95%CI: 1.42-18.5) than those with only one of the conditions. If our observations can be confirmed in larger studies, the findings will provide further evidence to support the role of IGF-I in breast cancer and the link between genetic polymorphism and cancer susceptibility.
Adult↗
Viagra: are anaesthetists rising to the challenge?
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Anesthesia, General↗
The effects of rigid collar placement on intracranial and cerebral perfusion pressures.
Rigid collars are routinely used to immobilise the cervical spine during early management of trauma victims until spinal injury is excluded. Spinal injuries commonly coexist in patients with severe head injury, and there is still uncertainty as to whether application of a rigid collar may adversely affect intracranial pressure. The aim of this study was to examine this effect by applying rigid collars to patients with traumatic head injury. The results showed a significant rise from the baseline intracranial pressure when the collars were applied (mean rise = 4.6 mmHg, p < 0.0001). The mean rise in intracranial pressure was greater in those patients with a baseline intracranial pressure > 15 mmHg compared to those with a baseline intracranial pressure < 15 mmHg (p < 0.05). Since there was no significant change in cardiorespiratory parameters during this time, venous compression in the neck seems a likely explanation for the effect observed. These findings suggest that in head-injured patients, rigid collars should be removed as soon as cervical spine injury has been excluded or, if this is delayed, an alternative method of spinal stabilisation considered.
Adolescent↗
Status epilepticus.
Status epilepticus is a medical emergency that requires rapid and vigorous treatment to prevent neuronal damage and systemic complications. Failure to diagnose and treat status epilepticus accurately and effectively results in significant morbidity and mortality. Cerebral metabolic decompensation occurs after approximately 30 min of uncontrolled convulsive activity, and the window for treatment is therefore limited. Therapy should proceed simultaneously on four fronts: termination of seizures; prevention of seizure recurrence once status is controlled; management of precipitating causes of status epilepticus; management of the complications. This article reviews current opinions about the classification, aetiology and pathophysiology of adult generalised convulsive status epilepticus and details practical management strategies for treatment of this life-threatening condition.
Adult↗
The effect of biofeedback in hypertension.
The purpose of this study was to determine the effectiveness of biofeedback in the treatment of stages 1 and 2 essential hypertension via meta-analytical methods. A utilization-focused integrative review was limited to adult randomized clinical trials, and study groups were categorized into biofeedback, active control, and inactive control. Both biofeedback and active control treatments resulted in a reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP). Only biofeedback (with related cognitive therapy and relaxation training) showed a significantly greater reduction in both SBP (6.7 mm Hg) and DBP (4.8 mm Hg) when compared with inactive control treatments. Nurses in practice settings should consider biofeedback therapy for their hypertensive clients.
Biofeedback, Psychology↗
Subcutaneous emphysema following the use of a high-pressure water jet.
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Adult↗
Five cases of severe cardiac disease in pregnancy: outcomes and costs.
The obstetric, medical and anaesthetic management of five pregnant patients with a variety of significant cardiac problems is briefly reviewed. The duration of hospitalisation, and the use of high dependency and intensive care are documented. Financial costs are estimated and their implications for the care of such patients during and following pregnancy are discussed.
Journal Article↗