Predisposition, subsequent fertility, and mortality of cows with uterine prolapse.
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Age Factors↗
Biomedical subjects
A M Murphy
Publications and source records attributed to A M Murphy.
Proximal trisomy of 1q mosaicism in a girl with hypertrophic cardiomyopathy associated with Wolff-Parkinson-White syndrome and multiple congenital anomalies.
We report an African American female who is mosaic for partial trisomy of 1q due to a direct duplication of 1q12 to 1q25. The child has hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome. The physical features include micrognathia, cleft palate, low set ears, posteriorly placed thumbs, and syndactyly of the second and third toes of both feet. Other abnormalities include intestinal malrotation, scoliosis, mental retardation, cerebral palsy, and hydrocephalus. There was also a selective deficiency of antibody responses to polysaccharide antigens. Proximal duplication of chromosome 1q is rare and has not been previously associated with hypertrophic cardiomyopathy. Most known gene disorders related to hypertrophic cardiomyopathy are autosomal dominant missense mutations in sarcomeric protein genes; however, none of the sarcomeric genes previously linked to hypertrophic cardiomyopathy are in this region. This finding thus highlights the possibility of additional genetic mechanisms for hypertrophic cardiomyopathy.
Abnormalities, Multiple↗
Regional cortical white matter reductions in velocardiofacial syndrome: a volumetric MRI analysis.
BACKGROUND: Velocardiofacial syndrome, caused by a microdeletion on chromosome 22q.11, is associated with craniofacial anomalies, cardiac defects, learning disabilities, and psychiatric disorders. To understand how the 22q.11 deletion affects brain development, this study examined gray and white matter volumes in major lobar brain regions of children with velocardiofacial syndrome relative to control subjects. METHODS: Subjects were ten children with velocardiofacial syndrome and ten age- and gender-matched unaffected children. Coronal images were acquired with a 3-D spoiled gradient echo series and partitioned into 124, 1.5-mm contiguous slices. A stereotaxic grid was used to subdivide brain tissue into cerebral lobes, which were segmented into gray, white, and CSF compartments using an algorithm based on intensity values and tissue boundaries. Nonparametric statistics were used to compare lobar volumes of gray and white matter. RESULTS: Analyses indicated that children with velocardiofacial syndrome had significantly smaller volumes in nonfrontal, but not frontal, lobar brain regions. Volume reductions affected nonfrontal white matter to a greater extent than nonfrontal gray matter. CONCLUSIONS: The presence of white matter reductions may be related to disturbances in myelination or axonal integrity in velocardiofacial syndrome. Further work is required to delineate the nature and extent of white matter anomalies, and to link them to variation in the neurocognitive and neuropsychiatric phenotype of velocardiofacial syndrome.
Adolescent↗
A piece of my mind: searching for Margaret.
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Breast Neoplasms↗
Induction of apoptosis in BCL-2-expressing rat prostate cancer cells using the Semliki Forest virus vector.
The Semliki Forest virus (SFV) vector is a transient RNA expression vector that has an inherent p53-independent apoptosis-inducing property. It is administered as recombinant SFV particles (rSFV) that undergo 1 round of replication only and express a gene cloned into the multicloning site. In our study we have investigated the ability of the SFV vector to induce apoptosis and inhibit tumour growth in rat prostate cancer (AT3-Neo) cells expressing the Bcl-2 oncogene (AT3-Bcl-2 cells), which normally inhibits apoptosis. rSFV expressing the enhanced green fluorescent protein (EGFP) gene (rSFV-EGFP), or recombinant RNA transfected into cells by electroporation, induced delayed apoptosis in AT3-Bcl-2 cells. SFV-mediated expression of a cloned pro-apoptotic Bax gene by the vector, however, enhanced apoptosis induction both in AT3-Bcl-2 cells and standard BHK-21 cells. Such Bax-expressing particles could be produced only at low titers compared to EGFP-expressing particles under standard conditions for particle production, but lowering the incubation temperature for particle production to 33 degrees C partially alleviated this effect. Bax-expressing particles were shown to inhibit the growth of AT3-Neo and AT3-Bcl-2 tumours in nude mice, as did high titre EGFP-expressing particles. It is concluded that SFV recombinant particles have potential as anti-tumour agents to treat apoptosis-resistant tumours.
Animals↗
The role of troponin abnormalities as a cause for stunned myocardium.
Myocardial stunning is a form of ischemic injury, which occurs with transient ischemia followed by re-establishment of flow, and which results in reversible cardiac dysfunction. There is evidence that the molecular defect in stunning is at the level of the contractile apparatus. Selective proteolysis of the myofilament protein, troponin I, appears to underlie the phenotype of stunning in some models, but other myofilament protein modifications may also have a role.
Actin Cytoskeleton↗
Maintained contractile reserve in a transgenic mouse model of myocardial stunning.
Cardiac excitation-contraction (E-C) coupling is impaired at the myofilament level in the reversible postischemic dysfunction known as "stunned" myocardium. We characterized tension development and calcium cycling in intact isolated trabeculae from transgenic (TG) mice expressing the major proteolytic degradation fragment of troponin I (TnI) found in stunned myocardium (TnI(1-193)) and determined the ATPase activity of myofibrils extracted from TG and non-TG mouse hearts. The phenotype of these mice at baseline recapitulates that of stunning. Here, we address the question of whether contractile reserve is preserved in these mice, as it is in genuine stunned myocardium. During twitch contractions, calcium cycling was normal, whereas tension was greatly reduced, compared with non-TG controls. A decrease in maximum Ca2+-activated tension and Ca2+ desensitization of the myofilaments accounted for this contractile dysfunction. The decrease in maximum tension was paralleled by an equivalent decrease in maximum Ca2+-activated myofibrillar ATPase activity. Exposure to high calcium or isoproterenol recruited a sizable contractile reserve in TG muscles, which was proportionately similar to that in control muscles but scaled downward in amplitude. These results suggest that calcium regulatory pathways and beta-adrenergic signal transduction remain intact in isolated trabeculae from stunned TG mice, further recapitulating key features of genuine stunned myocardium.
Adrenergic beta-Agonists↗
Acquisition of hearing aids and assistive listening devices among the pediatric hearing-impaired population.
Sufficient access to health care is of concern to the indigent population in the US and to their health care providers. This study was undertaken to elucidate the rate of the follow-up among lower socioeconomic hearing-impaired pediatric patients who had received a recommendation for hearing aids and/or assistive listening devices. Our question was, would the families' financial situation have a negative effect on the acquisition of hearing aids and assistive listening devices? Fifty patients, age 0-18 years, who had been seen in our clinic over 2 years were evaluated via a telephone survey. The survey consisted of seven questions, including whether or not the devices or aids were obtained, what type was purchased, where the device was being used, and the child's apparent performance with the device. Eighty-two percent of our patients were on TennCare, a state mandated Medicaid HMO system. Two-thirds of these TennCare patients are at or below the poverty level and the remaining one-third is either disabled or uninsurable according to the Aid for Dependent Children (AFDC) with indeterminate income. In addition the TennCare organization did not cover hearing amplification equipment for these children. The study showed that the majority of the patients did follow-up as recommended. Furthermore, this equipment is easily obtainable for the pediatric indigent population due to financial resources available in the community outside the mandated Medicaid system.
Adolescent↗
The acetabulum: sex assessment of prehistoric New Zealand Polynesian innominates.
With increasing urban development in New Zealand, prehistoric Polynesian skeletal remains are frequently being recovered. Since such material must often be reinterred quickly, it has become important that the sex of individuals be determined from the remains in a relatively short time. For this purpose, discriminant function analysis was utilised for sex determination of prehistoric adult New Zealand Polynesian innominates (21 male and 35 female). Maximum diameter of the acetabulum was measured and subjected to SPSS direct discriminant function analysis. Accuracy of sex determination ranged from 85.2% to 86.2%. Reduction in error over random assignment by sex ranged from 70% to 72%. The two discriminant functions derived will provide a useful tool for the assessment of human remains in the forensic and archaeological context because they incorporate a single measurement which can be taken on incomplete bones.
Acetabulum↗
Transgenic mouse model of stunned myocardium.
Stunned myocardium is a syndrome of reversible contractile failure that frequently complicates coronary artery disease. Cardiac excitation is uncoupled from contraction at the level of the myofilaments. Selective proteolysis of the thin filament protein troponin I has been correlated with stunned myocardium. Here, transgenic mice expressing the major degradation product of troponin I (TnI1-193) in the heart were found to develop ventricular dilatation, diminished contractility, and reduced myofilament calcium responsiveness, recapitulating the phenotype of stunned myocardium. Proteolysis of troponin I also occurs in ischemic human cardiac muscle. Thus, troponin I proteolysis underlies the pathogenesis of a common acquired form of heart failure.
Actin Cytoskeleton↗
A mouse model of myocardial stunning.
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Animals↗
Inhibition of human lung carcinoma cell growth by apoptosis induction using Semliki Forest virus recombinant particles.
We have utilised cell cultures and growth of tumours in nude mice to assess further the potential of the Semliki Forest virus (SFV) vector as a cancer therapy agent. This vector is a transient RNA-based expression vector, and we have previously shown that SFV and its derived vector can induce p53-independent apoptosis by expression of the nonstructural region of the virus genome. Apoptosis induction is therefore an inherent property of the vector and is not dependent on heterologous gene expression. SFV recombinant suicide particles (rSFV) were shown to induce apoptosis in H358a cells, which are human non-small cell lung carcinoma cells deleted in p53. EGFP-expressing rSFV also inhibited the growth of developing H358a spheroids. Direct injection of rSFV into H358a tumours subcutaneously implanted as xenografts in nu/nu mice inhibited tumour growth, and in some cases caused complete regression. It is concluded that tumour growth suppression induced by rSFV was due to apoptosis induction and that the vector has an inherent cell death-promoting and antitumour activity. These results, as well as previous work by other authors on targeting and immune stimulation using alphavirus vectors, indicate that SFV recombinant particles in particular have considerable potential for further exploitation as a cancer therapy agent.
Animals↗
Salicylic acid has a role in regulating gene expression during leaf senescence.
Leaf senescence is a complex process that is controlled by multiple developmental and environmental signals and is manifested by induced expression of a large number of different genes. In this paper we describe experiments that show, for the first time, that the salicylic acid (SA)-signalling pathway has a role in the control of gene expression during developmental senescence. Arabidopsis plants defective in the SA-signalling pathway (npr1 and pad4 mutants and NahG transgenic plants) were used to investigate senescence-enhanced gene expression, and a number of genes showed altered expression patterns. Senescence-induced expression of the cysteine protease gene SAG12, for example, was conditional on the presence of SA, together with another unidentified senescence-specific factor. Changes in gene expression patterns were accompanied by a delayed yellowing and reduced necrosis in the mutant plants defective in SA-signalling, suggesting a role for SA in the cell death that occurs at the final stage of senescence. We propose the presence of a minimum of three senescence-enhanced signalling factors in senescing leaves, one of which is SA. We also suggest that a combination of signalling factors is required for the optimum expression of many genes during senescence.
Arabidopsis↗
Penicillin failure in streptococcal tonsillopharyngitis: causes and remedies.
UNLABELLED: Penicillin administered for 10 days has been the treatment of choice for group A beta-hemolytic streptococcal tonsillopharyngitis since the 1950s. The bacteriologic failure rate of 10 days of penicillin therapy ranged from approximately 2 to 10% until the early 1970s. Beginning in the late 1970s bacteriologic and clinical failure rates with penicillin therapy began to increase steadily over time and are now reported to be approximately 30%. The primary cause of penicillin treatment failure in streptococcal tonsillopharyngitis may be lack of compliance with the 10-day therapeutic regimen. Other causes of penicillin treatment failure include reexposure to Streptococcus-infected family members or peers; copathogenicity, in which bacteria susceptible to a class of drugs are protected by other, colocalized bacterial strains that lack the same susceptibility; antibiotic-associated eradication of normal protective pharyngeal flora; and penicillin tolerance, whereby streptococcal bacteria repeatedly or continuously exposed to sublethal concentrations of antibiotic become increasingly resistant to eradication. Although 10 days of penicillin therapy is effective in the management of tonsillopharyngitis for many patients, multiple factors may, singly or together, cause treatment failure. A number of antibiotics, particularly the cephalosporins, have been demonstrated to be superior to penicillin at eradicating group A beta-hemolytic Streptococcus, and several are effective when administered for 4 to 5 days. CONCLUSIONS: Ten days of penicillin therapy may not be the best therapeutic choice for all pediatric patients. Other antibiotics, shortened courses of the cephalosporins in particular, may be preferable in some cases.
Cephalosporins↗
Comparison of a commercial enzyme-linked immunosorbent assay with immunofluorescence and complement fixation tests for detection of Coxiella burnetii (Q fever) immunoglobulin M.
A commercially available enzyme-linked immunosorbent assay (ELISA) for the diagnosis of Q fever (PanBio Coxiella burnetii immunoglobulin M [IgM] ELISA, QFM-200) was compared to the indirect fluorescent antibody test (IFAT) for C. burnetii IgM and the complement fixation test (CFT). The ELISA demonstrated 92% agreement with the reference method (IFAT), and gave a sensitivity of 99% (69 of 70 samples) and a specificity of 88% (106 of 121). Specificity can be increased with confirmation by IFAT. CFT was found to have a specificity of 90% (107 of 119), although it was lacking in sensitivity (73%; 51 of 70). No cross-reactivity was observed in the ELISA with serum samples from patients with mycoplasma (n = 6), chlamydia (n = 5), or legionella (n = 4) infections, although 2 of 5 patients with leptospirosis and 1 of 4 samples containing rheumatoid factor (RF) demonstrated positive results in the ELISA. Results indicate that the performance of the PanBio C. burnetii (Q fever) IgM ELISA (F = 187) is superior to that of CFT (F = 163), and consequently the ELISA should be a useful aid in the diagnosis of acute Q fever.
Antibodies, Bacterial↗
Variables influencing penicillin treatment outcome in streptococcal tonsillopharyngitis.
OBJECTIVE: To examine whether penicillin treatment success for group A beta-hemolytic streptococcal tonsillopharyngitis is influenced by patient age, number of days ill prior to initiation of treatment, number of prior episodes, season, total dosage (milligrams per kilogram), and frequency of administration (2 vs 3 times daily). METHODS: Four hundred seventy-eight children, adolescents, and young adults aged 2 to 21 years with acute symptoms compatible with the clinical diagnosis of group A beta-hemolytic streptococcal tonsillopharyngitis and a positive streptococcus rapid antigen detection test result were enrolled (intent-to-treat group). Patients were randomly assigned to receive penicillin V potassium, 250 mg 3 times daily (n = 239) or 500 mg 2 times daily (n = 239). Randomization was independent of patient body weight and treatment was for 10 days with both regimens. Follow-up examinations occurred, and cultures were obtained at 14 to 21 days after the initiation of antibiotic therapy; those with group A beta-hemolytic streptococcus isolated from a throat culture and who returned for follow-up were assessed for outcome (n = 359). RESULTS: Using a logistic regression analysis with a stepwise variable selection, we found the major variables associated with penicillin treatment success to be the number of days ill prior to initiation of treatment (P = .001; odds ratio, 1.55 [95% confidence interval, 1.2-2.1]) and the age of the child when infected (P = .004; odds ratio, 1.14 [95% confidence interval, 1.05-1.25]). The number of prior episodes within the preceding year, the season, the total daily penicillin dose (range, 8-76 mg/kg), and 2 vs 3 times daily dosing did not significantly alter treatment outcome. CONCLUSION: Treatment after 2 days of illness and of adolescent patients increases penicillin treatment success for group A beta-hemolytic streptococcal tonsillopharyngitis.
Adolescent↗
Fiduciary duties 101. Directors and officers have never been at greater risk.
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Administrative Personnel↗
Recurrent group A streptococcal tonsillopharyngitis.
OBJECTIVE: To examine the epidemiology and treatment of group A beta-hemolytic streptococcal (GABHS) recurrent tonsillopharyngitis in private pediatric practice. METHODS: This was a retrospective chart review study covering the time span 1975 to 1996 involving 2140 GABHS episodes. Diagnosis was based on acute clinical symptoms and laboratory confirmation (throat culture or positive rapid antigen detection test) of GABHS. RESULTS: Eighty percent (n=1721) of the episodes evaluated were treated with penicillin or amoxicillin; 352 (20.5%) of these were followed by a recurrence within 30 days and 519 (30.2%) within 60 days. GABHS recurrences within 30 days after penicillin/amoxicillin treatment rose from 9% in 1975 to 1979 to 25.9% in 1980 to 1984, 24.2% in 1985 to 1989, 22.4% in 1990 to 1994 and 25.9% in 1995 to 1996 (P < 0.02); 53.4% of the recurrences were associated with symptoms and signs of GABHS tonsillopharyngitis, 9.9% were asymptomatic and 36.7% could not be classified. Recurrences within 60 days after penicillin/ amoxicillin treatment rose from 10.7% in 1975 to 1979 to 38.7% in 1980 to 1984, 39.0% in 1985 to 1989, 31.7% in 1990 to 1994 and 37.5% in 1995 to 1996 (P < 0.001). Recurrent GABHS infections occurred more frequently in younger children (1 to 8 years of age, 21.3% recurrence rate) than in adolescents (13 to 19 years, 5% recurrence rate; P=0.002). Recurrences within 30 days occurred more often after therapy with penicillin (21.8% of 1581 episodes) than with cephalosporins (8.6% of 254 episodes) (P < 0.0001) or with macrolides (14.0% of 143 episodes, P=0.04). Recurrence rates were unaffected by patient gender or season of the year. CONCLUSIONS: Recurrent GABHS infections occur more frequently in the 1990s than the 1970s, occur more frequently in children younger than 8 years of age than in adolescents and occur more frequently after penicillin treatment than with alternative antibiotic therapy.
Adolescent↗