Compound heterozygosity for Hb S and Hb G-Copenhagen.
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Biomedical subjects
Publications and source records attributed to M Patterson.
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Cardiomyocytes lose the ability to proliferate after birth. Subsequently, irreversible cellular damage, e.g., during myocardial infarction, causes loss of functional properties and cell replacement by fibrotic tissue. It is, therefore, not surprising that cell replacement strategies such as cardiomyocyte transplantation in damaged myocardium or scar tissue has gained widespread interest. In other species such as mice, rats, and dogs, the technical feasibility of skeletal myoblast-, satellite cell-, and fetal cardiomyocyte engraftment into normal and diseased myocardium has been demonstrated by simple injection methods. Repeatedly, it has been shown that transplanted cells may survive for weeks within host myocardium and build intercellular connections such as gap junctions and desmosomes. In contrast, grafthost connections have not, as yet, been convincingly demonstrated. Hypothetically, cell transplants might exhibit the following functional properties: stabilization of diseased tissue to prevent structural remodeling; carrier for recombinant proteins, growth factors or drugs to induce molecular alterations of host myocardium; and improvement of regional and global myocardial function due to active contractility. However, clear evidence of coordinated contractility of transplanted cells, and, thus, of a clinically relevant therapeutical use of cardiomyocyte transplantation as a replacement strategy for damaged host cardiac cells, remains to be demonstrated.
BACKGROUND: Costs for large animal studies have escalated. Therefore there is a need to develop small animal models of non-ischemic cardiac failure and accurate non-invasive techniques that will allow serial quantitation of left ventricular function. OBJECTIVES: The purpose of our study was to determine the efficacy and reliability of adriamycin for inducing cardiomyopathy in rats. We hypothesized that high frequency transthoracic 2-dimensional and M-mode echocardiography would allow for serial testing of cardiac function in this small animal model. METHODS: Adriamycin was administered at a dose of 2.5 mg/kg intravenously once a week for 10 weeks in 54 rats. Transthoracic echocardiography by use of a 7.5 MHz transducer was performed in 19 rats at baseline and additionally at 12 weeks after beginning of adriamycin therapy to measure left ventricular dimensions and calculate fractional shortening. RESULTS: The mortality rate during the treatment period was 11%, but increased to 52% at 13 weeks. Transthoracic echocardiography provided adequate visualization of left ventricular dimensions and cardiac function in a parasternal short axis view. In follow-up echocardiography, pericardial effusion was detected in 8/19 rats (42%). Compared to baseline, end-diastolic diameters increased from 0.56 +/- 0.06 to 0.64 +/- 0.08 mm (p < 0.001), end-systolic diameters increased from 0.27 +/- 0.03 to 0.42 +/- 0.08 mm (p < 0.001), and fractional shortening decreased from 52.8 +/- 4.0 to 34.3 +/- 7.1% (p < 0.001) at 12 weeks. Electron microscopy in a subset of rats revealed cardiomyocyte degeneration, mitochondrial and sarcoplasmatic reticular edema, numerous intracellular vacuoles and 'onion-ring' shaped mitochondrial cristae, characteristic for adriamycin cardiotoxicity in human patients. CONCLUSION: Adriamycin at an intravenous dose of 2.5 mg/kg over 10 weeks can be used to create a reliable model of non-ischemic dilated cardiomyopathy with a high success rate. For in-vivo diagnostic purposes, transthoracic echocardiography provides a reliable technique to non-invasively assess cardiac function quantitatively and qualitatively in follow-up studies in rat cardiomyopathy. This small animal model can easily be used for testing new therapeutic strategies in cardiac failure.
The early outcome for severely injured patients has improved in the last 20 years, but the level of continuing long term disability in such patients is not known. A large cohort of severely injured patients (ISS > 15) were interviewed and examined approximately 5 years following their injury. We present the preliminary results which show that only 30 per cent had made a full recovery, and that an alarming 47 per cent remain with moderate, severe or very severe disabilities. A large proportion (45%) of the persisting disability is due to pelvic and limb injury (74 per cent if brain and spinal cord injuries are excluded). This study reflects initial treatment in 13 District General Hospitals and one Teaching Hospital in a single geographical region in 1989 and 1990, and is the first such study in the UK. We conjecture whether more aggressive and specialized treatment and rehabilitation, especially of orthopaedic injuries, would improve these disappointing results.
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Posterior patterning in the Drosophila embryo requires the action of Nanos (Nos) and Pumilio (Pum), which collaborate to regulate the translation of maternal hunchback (hb) mRNA. Previous work demonstrated that Pum recognizes sites in the 3' UTR of hb mRNA. In this report, we first define the RNA-binding domain of Pum and then show that residues essential for translational repression are embedded within this domain. We also show that Nos and Pum can repress cap-independent translation from an internal ribosome entry site (IRES) in vivo, suggesting that they act downstream of the initial steps of normal, cap-dependent translation.
The Internet could change the lives of average citizens as much as did the telephone in the early part of the 20th century and television in the 1950s and 1960s. Researchers and social critics are debating whether the Internet is improving or harming participation in community life and social relationships. This research examined the social and psychological impact of the Internet on 169 people in 73 households during their first 1 to 2 years on-line. We used longitudinal data to examine the effects of the Internet on social involvement and psychological well-being. In this sample, the Internet was used extensively for communication. Nonetheless, greater use of the Internet was associated with declines in participants' communication with family members in the household, declines in the size of their social circle, and increases in their depression and loneliness. These findings have implications for research, for public policy and for the design of technology.
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Ninety-three patients with panic disorder and mild or no agoraphobia were treated for their panic disorder by using either 11 sessions of individual cognitive-behavior therapy or imipramine. Before and after treatment, their panic disorder symptomatology was assessed, and a self-report measure was administered to measure personality disorder characteristics [Klein et al., 1990: Wisconsin Personality Disorders Inventory]. In addition, some patients received this personality assessment again after six monthly maintenance sessions. Both treatments were equally effective in reducing panic disorder symptomatology, and both treatments had a positive influence on personality disorder characteristics. Personality disorder characteristics did not predict treatment outcome in either group. The implications of the findings for the assessment of personality and the treatment of panic disorder are discussed.
BACKGROUND: The value of routine skull radiography as a method of predicting intracranial injury is controversial. We aimed to assess the effectiveness of skull radiography by prospectively studying head-injured children admitted to a children's hospital that serves an urban population. METHODS: Over a 2-year period, 9269 children attended our accident and emergency department with head injury, and 6011 were referred for skull radiography. All children who were admitted to hospital or had a skull fracture (n = 883) were included in the study. Computed tomography (CT) was done in children with skull fractures on radiography and in those without fractures if there were neurological indications. FINDINGS: Radiographs showed 162 fractures (2.7% of all radiographs and 18% of study group radiographs). Staff in the accident and emergency department missed 37 (23%) fractures. CT scan was done on 156 children, of whom 107 had a skull fracture. 23 children were found to have intracranial injuries on CT. The presence of neurological abnormalities had a sensitivity for identification of intracranial injury of 91% (21 of 23) and a negative predictive value of 97%. The corresponding values for skull fracture on radiography were 65% (15 of 23) and 83%. Four children died, of whom only one had a skull fracture. INTERPRETATION: In children, severe intracranial injury can occur in the absence of skull fracture. Skull radiography is not a reliable predictor of intracranial injury and is indicated only to confirm or exclude a suspected depressed fracture or penetrating injury, and when non-accidental injury is suspected, including in all infants younger than 2 years. Clinical neurological abnormalities are a reliable predictor of intracranial injury. If imaging is required, it should be with CT and not skull radiography.
We present a case of beta-thalassemia intermedia involving a 13-year-old boy of Northern European descent. His mother, father and older sister have normal hematologic indices. Molecular studies demonstrate that the proband carries a novel mutation of the beta-globin gene initiation codon (ATG-->AAG) which should give rise to beta(0)-thalassemia trait. The possibility of non-paternity was excluded, indicating that the novel mutation was the result of a de novo event. A review of the literature indicates that mutations involving the beta-globin gene initiation codon can give rise to a more severe phenotype than is generally associated with most other beta(+) or beta(0) mutations.
CY1503, an analogue of sialyl-Lewisx, is an inhibitor of the selectin adhesion molecules. CY1503 has been found to limit myocardial infarct size in canine and feline models. However, the effect of CY1503 on the "no-reflow" phenomenon is still unknown. Anesthetised rabbits were subjected to 30 min of coronary artery occlusion and 4 h of reperfusion. Protocol 1: after 27 min of ischemia, rabbits were randomised to an iv bolus of either CY1503 (30 mg/kg) (n=9) or saline (n=9). Protocol 2: rabbits were randomly given two iv boluses of CY1503 (30 mg/kg) (n=6) or saline (n=6), administered after 10 and 25 min of ischemia. Protocol 3: after 27 min of ischemia rabbits were randomly given an iv bolus of CY1503 (30 mg/kg) (n=6) and infusion of 20 mg/kg over 4 h or saline bolus+infusion (n=6). Regional myocardial blood flow (RMBF) was assessed after 30 min and 4 h of reperfusion. The risk zone (RZ) was assessed by blue dye and the necrotic zone (NZ) by tetrazolium staining. RMBF: protocol 1: RMBF in the RZ was 2.19+/-0.33 v 2. 34+/-0.34 ml/g/min in CY1503 and controls at 30 min (P=0.75), and 0. 43+/-0.07 v 0.41+/-0.08 at 4 h of reperfusion (P=0.85). The corresponding results for protocol 2 were 1.77+/-0.29 v 1.53+/-0.34 at 30 min (P=0.61) and 0.53+/-0.16 v 0.91+/-0.55 at 4 h (P=0.53). RMBF in RZ in protocol 3 were 1.52+/-0.25 v 1.32+/-0.20 at 30 min (P=0.56) and 0.30+/-0.05 v 0.29+/-0.09 (P=0.90) after 4 h of reperfusion. The RZ was similar in both groups in all protocols. The NZ/RZ ratio was comparable in the CY1503 and control group in all three protocols (0.32+/-0.04 v 0.37+/-0.06, 0.37+/-0.08 v 0.33+/-0. 07, and 0.51+/-0.05 v 0.38+/-0.05 in protocols 1, 2, and 3, respectively). CY1503 did not limit infarct size or prevent the "no-reflow" phenomenon in the rabbit.
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Nine monoclonal antibodies (mabs) have been produced against excretory-secretory products (ES) of adult male Onchocerca gibsoni. These mabs fail to interact with the highly cross-reactive phosphorylcholine (PC) group and with ES of the related rodent filarial parasites Acanthocheilonema viteae and Litomosoides carinii. Eight of the mabs are of the IgG isotype: 1 is an IgM. Three of the mabs, OGMES 4, 9, and 10, were each found by immunoprecipitation/SDS-PAGE analysis of [3H] leucine-labeled ES, to recognize a triplet of polypeptides of molecular weight 120, approximately 210, and approximately 260 kDa. No recognition was observed by any mab when [3H] glucosamine was employed as the radiolabel for ES. Western blotting employing [125I] as indicator system demonstrated that OGMES 7 recognized a molecule of 27 kDa, and OGMES 1, a molecule of approximately 210 kDa, albeit faintly. These mabs may be of value to researchers working on the isolation, characterization, and detection in the bloodstream of Onchocerca volvulus ES.