Identification of murine CBF alpha1, a runt domain transcription factor, as a putative Myc collaborator in T cell lymphoma.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M O'Hara.
Explore the source record for details and available documents.
Report of a case of a mycotic pseudoaneurysm of the ascending thoracic aorta occurring in the absence of surgical or blunt trauma in a patient who presented with purulent pericarditis. Surgical pericardial drainage was required, which revealed Staphlococcal aureus. Subsequent transesophageal echocardiogram demonstrated a 4 cm x 4 cm pseudoaneurysm of the posterior wall of the aorta above the sinotubular junction. The patient refused surgical correction of the aortic pseudoaneurysm and was successfully managed with antibiotic therapy.
BACKGROUND: Thromboembolism and valve-related death are major complications associated with prosthetic valve implants, but it is difficult to evaluate the relative incidence of these complications based on studies in which the implantation of only one valve is reported from any given institution. We therefore report the outcome of patients implanted at our institution during the same time period with either the recently released CarboMedics (CM) or the St. Jude Medical (SJ) valve prostheses. METHODS: Between October 1994 and January 1996, 245 consecutive patients received either SJ (116 patients) or CM (129 patients) valves at our institution. Follow up of these patients was 99.6% complete, for a total of 318.5 cumulative patient-years (median follow-up, 1.4 years). RESULTS: The 30-day mortality rates for SJ and CM implants were 3.4% and 3.1%, respectively. Actuarial survival and freedom from valve related mortality rates at 1.5 years for SJ and CM valves were 94%+/-2% versus 86%+/-3% (p = 0.03) and 100% versus 94%+/-2% (p = 0.005), respectively. There was no structural valve failure for either implant, but there were five thrombosed valves in the CM group and none in the SJ group (p = 0.04). All thrombosed valves were mitral (four mitral valve replacement, one aortic and mitral valve replacement). Two of the thrombosed valves were successfully explanted, whereas the three remaining patients died. Freedom from a thromboembolic event in the mitral position at 1.5 years, including thrombosed valves was 97%+/-3% and 83%+/-5% for SJ and CM valves, respectively (p = 0.04). CONCLUSIONS: The results of this study suggest that further evaluation of thromboembolic outcomes after CM compared with SJ valve implantation is warranted.
OBJECTIVES: The obligatory hemodilution resulting from crystalloid priming of the cardiopulmonary bypass circuit represents a major risk factor for blood transfusion in cardiac operations. We therefore examined whether retrograde autologous priming of the bypass circuit would result in decreased hemodilution and red cell transfusion. METHODS: Sixty patients having first-time coronary bypass were prospectively randomized to cardiopulmonary bypass with or without retrograde autologous priming. Retrograde autologous priming was performed at the start of bypass by draining crystalloid prime from the arterial and venous lines into a recirculation bag (mean volume withdrawal: 880 +/- 150 ml). Perfusion and anesthetic techniques were otherwise identical for the two groups. The hematocrit value was maintained at a minimum of 16% and 23% during and after cardiopulmonary bypass, respectively, in all patients. Patients were well matched for all preoperative variables, including established transfusion risk factors. Subsequent hemodynamic parameters, pressor requirements, and fluid requirements were equivalent in the two groups. RESULTS: The lowest hematocrit value during cardiopulmonary bypass was 22% +/- 3% versus 20% +/- 3% in patients subjected to retrograde autologous priming and in control patients, respectively (p = 0.002). One (3%) of 30 patients subjected to retrograde autologous priming had intraoperative transfusion, and seven (23%) of 30 control patients required transfusion during the operation (p = 0.03). The number of patients receiving any homologous red cell transfusions in the two groups during the entire hospitalization was eight of 30 (27%; retrograde autologous priming) versus 16 of 30 (53%; control) (p = 0.03). CONCLUSIONS: These data suggest that retrograde autologous priming is a safe and effective means of significantly decreasing hemodilution and the number of patients requiring red cell transfusion during cardiac operations.
This nonrandomised retrospective case-comparison survey was based on the hypothesis that craniofacial morphometric features can be used to identify individuals at greater risk for having children with a cleft. The theory of aetiological heterogeneity suggests there may be differences according to gender and cleft type. From a completely ascertained sample of 286 children with cleft lip and/or palate born in the West of Scotland between 1 January 1980 and 31 December 1984, a sample of 83 parents of the children with non-syndromic clefts volunteered for lateral cephalometric examination. A comparison group was derived from the archives of Glasgow Dental Hospital. Multivariate statistical analyses were applied to identify which parental craniofacial parameters, if any, determine predisposition to orofacial clefting. Compared to the male comparison group, the fathers of children with CL(P) were shown to have reduced mandibular and symphyseal areas (P < 0.001), reduced maxillary area (P < 0.01) and a shorter palatal length (P < 0.01). The cranial base angle was more acute (P < 0.01) and the cross-sectional area of the cranium on lateral skull radiographs was significantly smaller (P < 0.001). However, the occipital subtenuce was larger in the fathers (P < 0.05). The craniofacial morphology in the mothers of children with CL(P) was characterized by a longer mandible (P = 0.011), an increase in the anterior facial height (P < 0.05) and greater facial length (P < 0.01). Anterior cranial base and the clivus length were also larger in the mothers (P < 0.05). The cranial parameters showed a similar trend to the paternal group with a reduced cranial area (P < 0.01) and an increase in the occipital subtenuce length (P < 0.001). Different cephalometric parameters distinguish fathers from a male comparison group and mothers from their female counterparts. An awareness of these parameters might be of value in the prediction of liability to clefting and may prove to be important in the quest for clues to the pathogenesis of both CP and CL(P).
Under tremendous pressure to contain costs, most U.S. hospitals are radically altering the composition and skill mix of their staff, thinning their skilled registered nurse (RN) ranks, and often substituting them with minimally trained, lower paid, unlicensed assistive personnel (UAP). Twelve staff nurses were interviewed to illuminate the experience of working with UAP, who function largely in untested, expanded roles. Only two nurses viewed this experience positively; the rest were either opposed to or had strong reservations about UAP use. Confusion and emotional turmoil predominated as these nurses struggled to maintain safe, comprehensive care with the assistance of UAP who were often ambivalent and sometimes dangerously inept.
The til-1 locus was identified as a common retroviral integration site in virus-accelerated lymphomas of CD2-myc transgenic mice. We now show that viral insertions at til-1 lead to transcriptional activation of PEBP2alphaA (CBFA1), a transcription factor related to the Drosophila segmentation gene product, Runt. Insertions are upstream and in the opposite orientation to the gene and appear to activate a variant promoter that is normally silent in T cells. Activity of this promoter was detected in rodent osteogenic sarcoma cells and primary osteoblasts, implicating bone as the normal site of promoter activity. The isoforms encoded by the activated gene all encompass the conserved runt DNA-binding domain and share a novel N terminus different from the previously reported PEBP2alphaA products. Minor products include isoforms with internal deletions due to exon skipping and a novel C-terminal domain unrelated to known runt domain factors. The major isoform expressed from the activated til-1 locus (G1) was found to account for virtually all of the core binding factor activity in nuclear extracts from its corresponding lymphoma cell line. Another member of this gene family, AML1(CBFA2), is well known for its involvement in human hemopoietic tumors. These results provide evidence of a direct oncogenic role for PEBP2alphaA and indicate that the Myc and Runt family genes can cooperate in oncogenesis.
Golden retriever muscular dystrophy (GRMD) is an excellent model for the study of the efficacy of gene therapy in dystrophin deficient myopathies for there are many similarities between affected dogs and Duchenne muscular dystrophy (DMD) in boys. GRMD is not caused by deletion mutation but results from a point mutation in the consensus splice acceptor in intron 6 of the canine dystrophin gene. As a result exon 7 is skipped during processing of the GRMD dystrophin messenger RNA. We have developed a rapid test which makes direct use of exon 7 specific genomic PCR products. We have undertaken preliminary experiments on gene therapy using the mini-gene and the full length gene alone and in combination with lipofectin and/or the bacterial beta-galactosidase reporter gene Lac Z. Following direct injection of the Lac Z plasmid, either alone or with lipofectin, about 50% of the sites showed expression when biopsied some 14 days later. The beta-galactosidase activity was present in muscle and granulation tissue but was never abundant. Pups injected intraperitoneally with Lac Z were found to have positive material in their mesenteric lymph nodes, liver and spleen. Those injected with Lac Z and lipofectin also had positive material in the diaphragm, intercostal muscles and abdominal muscles, but again only a small amount of positive material was present at any of the sites. In animals directly injected into the muscle with the dystrophin mini-gene, half had positive staining for dystrophin in biopsies taken 14 days later. Of the 6 sites in the muscles of animals given the mini-gene and lipofectin only one had fibres positive for dystrophin when examined 14 days later. Six pups were injected directly with full-length gene construct and when biopsies were taken 10 days later two of the animals had strongly stained peripheries to a small number of fibres.
Explore the source record for details and available documents.
Syntactic bootstrapping was assessed in six children with normally developing language (NL) and six children with specific language impairment (SLI), ages 6 and 8, respectively. Children earned normal range non-verbal IQs and were matched by raw scores on a test of sentence comprehension. They were asked to listen to sentences containing novel verbs and to act out the meanings with toys. The SLI children earned reliably lower scores, but their errors suggested processing limitations rather than deficits in syntactic representation.
Moloney murine leukaemia virus (MoMLV) markedly accelerates thymic lymphoma development in mice carrying a transgene in which the human c-myc gene is linked to the CD2 locus control region. To investigate the mechanism of synergy and identify the genes which collaborate with myc in these clonal tumours, we analysed the sites of MoMLV insertion. Analysis of known viral integration loci revealed only a small number of insertions at bmi-1, pim-1 and ahi-1. Further cloning and hybridization analysis revealed a new common integration locus, designated til-1, which was occupied in 25 out of 77 lymphomas examined, with evidence of multiple clonal insertions in some cases. Mapping relative to established chromosomal markers in interspecific backcross mice located til-1 to mouse chromosome 17, distal to pim-1 and tic-1. These results suggest that the til-1 locus may harbour a novel myc-collaborating gene which acts as a target for activation in T cell lymphomas.
Activation of the c-myc oncogene and functional loss of the p53 tumour suppressor gene are among the most frequently recorded genetic lesions in neoplasia but their combined effect has not previously been investigated. By breeding together mice transgenic for human c-myc (CD2-myc) and mice carrying an inactive p53 allele (p53-/-) we found that these genetic lesions act synergistically in vivo. Offspring carrying the CD2-myc transgene and the homozygous p53 null mutation (p53-/-/CD2-myc) were viable but developed thymic lymphomas with dramatically increased frequency and reduced latency compared to both parental groups. The tumour phenotype was similar to that previously recorded for CD2-myc mice (predominantly CD3+, CD4+8+) but tumour clonal complexity and metastasis was significantly greater in the p53-/-/CD2-myc mice. In contrast, no significant increase in tumour incidence was seen in p53+/-/CD2-myc vs p53+/+/CD2-myc mice over a 6 month observation period. However, the loss of wild type p53 in a proportion of tumour cells in p53+/-/CD2-myc lymphomas suggests that wild type allele loss can occur as a late progression step rather than an initiating step in these tumours. We suggest that p53 loss of function may collaborate with the CD2-myc transgene at more than one stage in thymic lymphoma development.
To assess the correspondence between ideal and actual monitoring for disease-modifying anti-rheumatic drugs and the reasons for protocol failure, and the sharing of this task between primary and secondary care, we studied 249 patients with rheumatoid arthritis in a single district general hospital. Ideal monitoring protocols were derived from data sheets and from the rheumatological literature. Overall the ideal protocol was followed in 65% of cases: this ranged from 93% for methotrexate to 26% for sodium aurothiromalate. Most of the monitoring was done in general practice (e.g. 67% of all blood tests) and, with some exceptions, general practitioners (GPs) were willing to perform this task. However, many GPs reported logistic differences with specimen transfer and expressed the need for more information and support. Poor communication between hospital, patient and GP was also found to be a cause of protocol failure.
OBJECTIVE: To review the findings of interdisciplinary team evaluations of children who disclosed sexual abuse via facilitated communication. DESIGN: Case series. SETTING: Tertiary care hospital outpatient child sexual abuse program in central New York. PATIENTS: Between January 1990 and March 1993, 13 children who disclosed sexual abuse via facilitated communication and were referred to a university hospital child abuse referral and evaluation center. The range of previously determined developmental diagnosis included mental retardation, speech delay, and autism. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Medical records were reviewed for (1) disclosure, (2) physical evidence, (3) child's behavioral and medical history, (4) disclosures by siblings, (5) perpetrator's confession, (6) child protective services determinations, and (7) court findings. RESULTS: Four children had evidence of sexual abuse: two had physical findings consistent with sexual abuse, one also disclosed the allegation verbally, and one perpetrator confessed. CONCLUSIONS: These results neither support nor refute validation of facilitated communication. However, many children had other evidence of sexual abuse, suggesting that each child's case should be evaluated without bias.
Replantation of amputated parts and emergency microvascular repair of injured extremities are the two most common applications of clinical microsurgery. A major complication of emergency referral of such cases is the existence of the other injuries unrecognized at the time of initial evaluation. We have reviewed this complication within a series of emergency microsurgical cases referred to this unit. Several reports examining this problem of missed injuries exist in the general trauma literature. To our knowledge this study is the first to look at this important problem in the context of acutely injured patients referred for emergency microsurgery. A retrospective analysis of patients referred to Davies Medical Center over a 7-year period was performed. Nine of 1100 patients (0.8%) transferred to our unit for microsurgical evaluation and treatment had unrecognized coexisting injuries that put those patients at high risk for injury-specific morbidity and demanded immediate changes in the original care planned at the time of referral. Brief case histories of these patients are outlined. We review the trauma literature of such injuries. A concise protocol elucidating the guidelines and pitfalls of emergency microsurgical referral is offered.
Explore the source record for details and available documents.
Left ventricular dysfunction during exercise is considered a relatively sensitive marker of ischemia in patients with coronary artery disease. The purpose of this study was to determine whether exercise-induced myocardial dysfunction was more severe in patients with angina than in patients with ischemia without angina. Seventy-seven patients with angiographically documented coronary artery disease and an abnormal left ventricular response to exercise were studied by means of gated blood pool imaging. The arteriographic and functional parameters of 24 patients with angina during exercise testing imaging. The arteriographic and functional parameters of 24 patients with angina during exercise testing were compared with those of 53 patients who were pain free at the time of the test. Both groups were similar with regard to rate of multivessel disease (50% vs 51%, p = NS) and prior myocardial infarction (46% vs 51%, p = NS), as well as age, sex, and history of angina. Mean global ejection fraction remained unchanged (but abnormal) in both groups of patients during exercise. Furthermore, evidence of new regional asynergy during exercise assessed by a five-point scoring system was found to be equally abnormal in the two groups. Results of this study suggest that the severity of exercise-induced global and regional left ventricular dysfunction is independent of the presence of absence of angina during exercise testing.
One microsurgical unit's experience with leech application to 67 patients is surveyed. Five illustrative cases are presented to explain strategies of leech use, and plans for future research are discussed.