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Biomedical subjects

A Mitchell

Publications and source records attributed to A Mitchell.

At least 127 records · Page 7Linked to original sources
PubMed1997

Determinants of transplant-related coronary calcium detected by ultrafast computed tomography scanning.

Coronary calcium detected by ultrafast computed tomography (CT) has been shown to be a marker of coronary artery disease in heart transplant recipients. The objective of this study was to examine the possible determinants of coronary calcium after heart transplantation. Over a 15-month period, 102 consecutive cardiac transplant recipients (mean age 53 years, 88 men) underwent ultrafast CT scanning of the heart, in addition to coronary angiography, to determine coronary calcium score on their annual follow-up (a median of 4.6 years [range 63 days to 9.1 years] after transplant). The following data were also recorded: the recipient's sex and date of birth, date of transplantation, date of ultrafast computed tomography and coronary angiography; recipient pretransplant diagnosis, history of diabetes mellitus and systemic hypertension, fasting lipid profile, immunosuppression, number of rejection episodes, and donor organ ischemic time. Forty six patients (45.1%) had total calcium scores >0 and 41 (40.2%) had at least 1 major coronary with angiographic narrowing >24%. On univariate analysis, coronary calcium was significantly associated with dyslipoproteinemia, total cholesterol was >6.0 mmol/L (240 mg/dl), triglycerides were >3.0 mmol/L (265 mg/dl), and lipoprotein(a) >30 mg/ dl; > or =25% angiographic disease was significantly associated with coronary calcium and dyslipoproteinemia. Logistic regression revealed that dyslipoproteinemia, systemic hypertension, and donor ischemic time were significant predictors of coronary calcium in transplanted hearts. We conclude that the prevalence of coronary calcium in heart transplant recipients is high and is related to recipient dyslipoproteinemia, systemic hypertension, and donor organ ischemic time.

Calcinosis↗
PubMed1997

Neoplastic transformation of the endocervix associated with downregulation of lactoferrin expression.

The incidence of cervical adenocarcinomas in young women over the last two decades has increased. Even with increasing knowledge of the role of human papillomavirus in the etiology of adenocarcinoma of the cervix, there is a paucity of data concerning the genetic and epigenetic factors that contribute to the histologic features and biologic behaviors of these tumors. Lactoferrin is a basic glycoprotein found in human milk, secondary granules of neutrophils, and many body secretions, and it has been associated with carcinogenesis of the endometrium, breast, and lymphoid systems. In this study, we examined the expression of lactoferrin in normal human endocervical epithelium and in cervical adenocarcinomas in relation to proliferative index, steroid receptor status, p53 protein expression, and apoptosis. Immunohistochemical and in situ studies demonstrated that lactoferrin protein and mRNA were strikingly downregulated upon neoplastic transformation of the endocervix as early as in adenocarcinoma in situ when compared with the prominent expression exhibited by the normal cervical epithelium. Furthermore, neoplastic transformation of endocervical epithelial cells was accompanied by a pronounced stimulation of proliferation and a substantial reduction in the expression of the estrogen and progesterone receptors and p53 but little or no change in the number of apoptotic cells. In conclusion, we identified lactoferrin as a novel cancer-specific marker of endocervical adenocarcinomas that may be useful in the early detection of the disease, prediction of prognosis, and the development of new therapeutic modalities.

Adenocarcinoma↗
PubMed1997

Acute colonic surgery and unrecognized hypothyroidism: a warning. Report of six cases.

PURPOSE: This study was designed to highlight the significant morbidity related to undetected hypothyroidism in the elderly who are undergoing emergency surgery. METHOD: Case reports of six patients who presented with acute colonic surgical conditions are reviewed. RESULTS: Six cases of undetected hypothyroidism in a group of elderly patients was unmasked at the time of surgery for acute colonic conditions or in the perioperative period. These patients experienced increased morbidity, but once detected and treated, all but one had an uneventful recovery. CONCLUSION: Unrecognized hypothyroidism may lead to unnecessary surgery or even a potentially fatal outcome. A heightened awareness of this not so uncommon entity is mandatory.

Aged↗
PubMed1997

Effects of chronic high-rate electrical stimulation on the cochlea and eighth nerve in the deafened guinea pig.

This study was undertaken to examine the effects of chronic high-rate stimulation on the eighth nerve and cochlea. Fifty-four male pigmented guinea pigs were deafened and implanted with single ball electrodes in scala tympani. Four groups of animals received chronic electrical stimulation at a level of 5 microCol/cm2/ph for 1000 h as follows: Group A: 1000 Hz, 100 microseconds/ph duration, 100 microA peak; Group B: 250 Hz, 100 microseconds/ph duration, 100 microA peak; Group C: 2750 Hz, 36 microseconds/ph duration, 250 microA peak; Group D: 250 Hz, 400 microseconds/ph duration, 25 microA peak. Also, two control groups received 20 min stimulation during weekly electrically evoked auditory brainstem response (eABR) measurement (Group E) and about 5 s stimulation (Group F) during a brief eABR 3 day postimplantation and at perfusion. On Day 50, animals were perfused, midmodiolar sections cut and a quantitative assessment of spiral ganglion cells (SGC) performed. All stimulated subjects showed a similar decrease in eABR thresholds and dynamic range over time. No stimulation conditions induced pathology. All stimulation conditions enhanced survival of SGCs compared to unimplanted ears and implanted non-stimulated ears (Group F). There were no statistically significant differences in SGC survival between any stimulated groups, including Group E stimulated once a week. In conclusion, high-rate stimulation, under the conditions of this study, provides no additional risks and the same benefits to SGC survival as low-rate stimulation.

Animals↗
PubMed1997

The prognostic significance of non-invasive cardiac tests in heart transplant recipients.

The long-term mortality and morbidity of cardiac transplant recipients is related to their subsequent development of accelerated coronary atheroma and its complications. Coronary angiography was compared with non-invasive clinical assessment to see which was better in predicting clinical outcome. Ninety-one consecutive transplant recipients (mean age 53 years), in whom investigations had been performed (exercise electrocardiography, rest and exercise radionuclide ventriculography, 2-D echocardiography and coronary angiography), were followed up for a mean period of 2.1 years. Eighteen patients had 31 cardiac events. There were five cardiac-related deaths, 17 myocardial infarctions and/or onsets of heart failure, eight percutaneous transluminal coronary angioplasties and one coronary artery bypass graft. With cardiac event-free survival as the dependent variable and the results of the above investigations as independent variables, a series of univariate, bivariate and regression analyses were performed. On bivariate analysis, an echocardiographic ejection fraction of > 60% significantly predicted both survival free of myocardial infarction and/or heart failure and/or cardiac death and survival free of any cardiac event (P = 0.001 for both). Absence of coronary angiographic disease (both of < 25% and of < 50% luminal narrowing in any vessel) significantly predicted survival free of any cardiac event (P = 0.00004 and 0.015, respectively). Neither radionuclide ventriculography nor exercise electrocardiography were significant predictors of event free survival. In conclusion, echocardiography is at least as important as coronary angiography in the follow-up and prognostic assessment of cardiac transplant recipients.

Cause of Death↗
PubMed1997

Phylogenetic utility of elongation factor-1 alpha in noctuoidea (Insecta: Lepidoptera): the limits of synonymous substitution.

To test its phylogenetic utility, nucleotide sequence variation in a 1,240-bp fragment of the elongation factor-1 alpha (EF-1 alpha) gene was examined in 49 moth species representing the major groups of the superfamily Noctuoidea. Both parsimony and distance analyses supported the monophyly of nearly all groups for which there are clear morphological synapomorphies. Clades of subfamily rank and lower, probably mid-Tertiary and younger, were strongly supported. The third codon position contains 88% of variable sites, and approaches saturation at approximately 20% sequence divergence, possibly due to among-site rate heterogeneity and composition bias; higher divergences occur only in association with shifts in composition. Surprisingly, the few nonsynonymous changes appear no more phylogenetically reliable than synonymous changes. Signal strength for basal divergences is weak and fails to improve with character weighting; thus, dense taxon sampling is probably needed for strong inference from EF-1 alpha regarding deeper splits in Noctuoidea (probably early Tertiary). EF-1 alpha synonymous changes show promise for phylogeny reconstruction within Noctuidae and other groups of Tertiary age.

Animals↗
PubMed1997

Identification of the FKS1 gene of Candida albicans as the essential target of 1,3-beta-D-glucan synthase inhibitors.

Pneumocandins and echinocandins are fungicidal antibiotics, currently in clinical development, that inhibit 1,3-beta-D-glucan synthase (GS) in several human fungal pathogens. We have identified a gene from the diploid organism Candida albicans that encodes a target of these inhibitors. A 2.1-kb portion of this gene, designated CaFKS1, has significant homology to the Saccharomyces cerevisiae FKS1 and FKS2 genes, which encode partially functionally redundant subunits of GS. To evaluate the role of CaFkslp in susceptibility to echinocandins, we disrupted CaFKS1 on one homolog each of the spontaneous pneumocandin-resistant C. albicans mutants CAI4R1, NR2, NR3, and NR4. These mutants had been selected previously on agar plates containing the pneumocandin L-733,560. The clones derived from this transformation were either resistant (Ech[r]) or fully sensitive (Ech[s]) to inhibition by L-733,560 in both liquid broth microdilution and in vitro GS assays. The site of plasmid insertion in the transformants was mapped by Southern blot analysis, using restriction site polymorphisms in the CaFKS1 gene to distinguish between the two alleles (designated CaFKS1h and CaFKS1b). For strains CAI4R1 and NR2, the CaFKS1b allele was disrupted in each Ech(r) transformant; for strain NR4, CaFKS1h was disrupted in each Ech(r) transformant. We conclude that (i) strains CAI4R1, NR2, and NR4 are heterozygous for a dominant or semidominant pneumocandin resistance mutation at CaFKS1, (ii) drug resistance mutations can occur in either CaFKS1 allele, and (iii) CaFks1p is a target of the echinocandins. For transformants of strain NR3, all the clones we analyzed were uniformly Ech(r), and only the CaFKS1h allele, either in disrupted or wild-type form, was detected on genomic Southern blots. We believe gene conversion at the CaFKS1 locus may have produced two Cafks1h alleles that each contain an Ech(r) mutation. Transformants derived from the mutants were analyzed for susceptibility to pneumocandin treatment in a mouse model of disseminated candidiasis. Strains heterozygous for the resistant allele (i.e., C. albicans CAI4R1, NR2, and NR4) were moderately resistant to treatment, while strains without a functional Ech(s) allele (i.e., strain NR3 and derivatives of strain CAI4R1 with the disruption plasmid integrated in the Ech[s] allele) displayed strong in vivo echinocandin resistance. Finally, we were unable to inactivate both alleles at CaFKS1 by two-step integrative disruption, suggesting that CaFks1p is likely to be an essential protein in C. albicans.

Amino Acid Sequence↗
PubMed1997

Patient education in TENS pain management.

Chronic pain affects around 11% of the population and pain management costs the NHS Pounds 270 million a year. Conclusions are mixed but many studies have found TENS to be effective in the management of chronic pain, especially if used correctly and for a sufficient duration. The nurse's role as patient educator can be a strong influence on the therapy's success.

Humans↗
PubMed1996

Eomesodermin, a key early gene in Xenopus mesoderm differentiation.

Eomesodermin (Eomes) is a novel Xenopus T-domain gene. In normal development, it is expressed in mesodermal cells in a ventral-to-dorsal gradient of increasing concentration. It reaches its peak expression 1-2 hr before any other known panmesodermal gene. It is strongly inducible by normal vegetal cells and by mesoderm-inducing factors. Ectopic expression of Eomes in animal caps induces the transcription of nearly all mesodermal genes in a concentration-dependent way. Overexpression of Eomes dorsalizes ventral mesoderm, inducing gsc and changing cell fate to muscle and notochord. Blocking the function of Eomes causes gastrulation arrest and defective mesoderm-dependent gene activation. We propose that Eomes fulfills an essential function in initiating mesoderm differentiation and in determining mesodermal cell fate.

Activins↗
PubMed1996

Structural and functional properties of full-length and truncated human proapolipoprotein AI expressed in escherichia coli.

Utilizing the Escherichia coli/pGex vector expression system incorporating a thrombin cleavage site, full-length (residues -6-243) and truncated forms of proapolipoprotein AI (proapoAI), terminating at amino acid residues 222, 210, 150, and 135, were purified to levels of at least 5 mg/L, after thrombin cleavage. Assessed by circular dichroism, the helical contents of L-alpha-dimyristoylphosphatidylcholine-associated forms of human plasma-derived apolipoprotein AI (apoAI) and recombinant proapoAI were comparable, being 69% and 65%, respectively. Circular dichroism measurements of the lipid-associated complexes of the truncated forms showed that between the sequence of residues 150-222 no additional helicity was gained until the carboxyl-terminal sequence was present in the molecule, indicating that the carboxyl terminus of the protein is required for the formation of helix within this central region. While tryptophan residues were more than 86% accessible, as assessed by iodide quenching, in the two truncated forms, proapoAI-6-135 and proapoAI-6-150, for both free and complexed protein, this figure fell to about 50% for full-length recombinant proapoAI, further indicating the influence of the carboxyl terminus on the structure of the whole protein. While cross-linking human plasma apoAI in solution with dithiobis-(succinimidyl propionate) revealed high molecular weight oligomers by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, recombinant proapoAI did not strongly form complexes larger than trimers. None of the truncated proapoAI molecules formed oligomers larger than trimers. The shortest form, proapoAI-6-135, only dimerized. Initial results from lecithin:cholesterol acyltransferase activation (apoAI peptide concentration 0.2 microM) indicated that truncation of the 21 carboxy-terminal amino acids resulted in a drop of approximately 53% in activation and 33 residues a drop of 67% relative to the full-length protein. Overall these results indicate the important influence of the carboxyl terminus on the structure of apoAI.

Apolipoprotein A-I↗
PubMed1996

An experimental system for analyzing response to a morphogen gradient.

A recently described experimental system for analyzing the mode of action of a morphogen gradient involves the in situ hybridization of sectioned tissue constructs. In these constructs, a source of activin signaling induces the transcription of several mesodermal genes in blastula animal caps, according to the position of cells in a concentration gradient. New experiments show that activin-loaded beads emit a signal for only 2 hr and that the same cell can be induced to express different genes. We determine the position in the gradient and the time after the start of activin signaling at which early genes, including Mix1, Xpo, Xwnt8, Xchd, and Xlim1, are activated, relative to the previously tested genes Xbra and Xgsc.

Activins↗
PubMed1996

Postdischarge geriatric assessment of hospitalized frail elderly patients.

BACKGROUND: The diffusion of comprehensive geriatric assessment services has been rather limited in North America partly because of reimbursement and organizational constraints. OBJECTIVE: To evaluate the impact of a comprehensive geriatric assessment intervention for frail older patients that is started before hospital discharge and is continued at home. METHODS: Patients older than 65 years were selected who had either unstable medical problems, recent functional limitations, or potentially reversible geriatric clinical problems. Patients (n = 354) were randomly assigned to either the intervention group or a control group. Information on survival, readmissions, nursing home placement, medication use, and health status was collected at 30 and 60 days after hospital discharge. RESULTS: No differences were observed between the two treatment groups in survival, hospital readmission, or nursing home placement by 60 days. After adjustment for baseline characteristics, no significant differences were observed between the two groups on measures of physical functioning, social functioning, role limitations, health perceptions, pain, mental health, energy and/or fatigue, health change, or overall well-being. CONCLUSIONS: Although efficacy has been demonstrated for some forms of comprehensive geriatric assessment, the types of services that are easier to establish (inpatient consultation services and ambulatory assessment) have not been shown to improve outcomes. Our results indicate that outcomes are unaffected by a limited form of comprehensive geriatric assessment begun in the hospital and completed at home. Further efforts are needed to develop and to evaluate realistic approaches to comprehensive geriatric assessment.

Aged↗
PubMed1996

Familial temporal lobe epilepsy: a common disorder identified in twins.

We describe a new syndrome of familial temporal lobe epilepsy in 38 individuals from 13 unrelated white families. The disorder was first identified in 5 concordant monozygotic twin pairs as part of a large-scale twin study of epilepsy. When idiopathic partial epilepsy syndromes were excluded, the 5 pairs accounted for 23% of monozygotic pairs with partial epilepsies, and 38% of monozygotic pairs with partial epilepsy and no known etiology. Seizure onset for twin and nontwin subjects usually occurred during adolescence or early adult life. Seizure types were simple partial seizures with psychic or autonomic symptoms, infrequent complex partial seizures, and rare secondarily generalized seizures. Electroencephalograms revealed sparse focal temporal interictal epileptiform discharges in 22% of subjects. Magnetic resonance images appeared normal. Nine affected family members (24%) had not been diagnosed prior to the study. Pedigree analysis suggested autosomal dominant inheritance with age-dependent penetrance. The estimated segregation ratio was 0.3, indicating an overall penetrance of 60% assuming autosomal dominant inheritance. The mild and often subtle nature of the symptoms in some family members may account for lack of prior recognition of this common familial partial epilepsy. This disorder has similarities to the El mouse, a genetic model of temporal lobe epilepsy with a major gene on mouse chromosome 9, which is homologous with a region on human chromosome 3.

Adolescent↗