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Biomedical subjects

A Mitchell

Publications and source records attributed to A Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed1994

Analysis of centromere structure in the fly Megaselia scalaris (Phoridae, Diptera) using CREST sera, anti-histone antibodies, and a repetitive DNA probe.

We have used CREST anti-centromere sera, rabbit anti-histone antibodies, and repetitive DNA analysis to study centromere structure in the fly Megaselia scalaris (Phoridae). In a panel of eight CREST sera, four were positive in immunofluorescence experiments for prekinetochores, ie centromeres in interphase nuclei. The access of the antibodies to CREST antigens may be compromised in the condensed state, since centromeres of prometaphase and metaphase chromosomes remained unstained. When Western blots of embryonic nuclei were probed with these four CREST sera, three of them showed a 17 kDa band. Human CENP-A, likewise recognized by the CREST sera, is a 17 kDa protein. The remaining sera were negative for centromeres although some detected centrosomes and non-histone chromosomal proteins not confined to the centromeres. The use of antibodies generated against histone H4 acetylated at four different sites of the N-terminal domain revealed that heterochromatic regions of M scalaris mitotic chromosomes, ie pericentric and NOR-associated segments, are hyperacetylated. This is at variance with a variety of other systems, where transcriptionally active chromatin is hyperacetylated. Finally, a repetitive 165 base pair fragment was isolated from genomic DNA of the fly and sequenced. An oligonucleotide from this sequence mapped to the centromere region of interphase nuclei and the pericentric regions of condensed chromosomes.

Animals↗
PubMed1994

Geriatric home assessment after hospital discharge.

OBJECTIVES: To evaluate the feasibility of an intervention involving post-discharge geriatric home assessment and follow-up and to describe the spectrum of significant clinical problems identified during the home assessment. DESIGN: Prospective observational study nested within a randomized controlled trial. SETTING: Inpatient service of a large academic medical center in Southern California. PATIENTS: There were 152 adults aged 65 or greater who had one or more specific risk factors for functional decline or increased mortality, who were awaiting discharge from the hospital, and who were assigned to the intervention arm of a randomized controlled trial of post-discharge comprehensive geriatric home assessment. MAIN RESULTS: During the home assessment, the gerontologic nurse practitioner (GNP) identified new or worsening problems in 150 patients (99%); 61 problems (eg, serum sodium 125 mg/dL; severe orthostatic hypotension) were considered by a reviewing physician to require urgent medical attention. Older age, non-white race, and new incontinence were associated independently with a greater number of findings (P < 0.05). Based on the findings, an interdisciplinary team made an average of 3.4 recommendations per patient; only two of 111 requests for written approval of recommendations were rejected. CONCLUSIONS: Post-discharge visitation by a GNP to patients at high risk is capable of detecting a high yield of important and potentially reversible clinical problems. This multidisciplinary approach is acceptable to physicians. Research is needed to identify additional links between short hospital stays, impairment or instability at discharge, and adverse outcomes.

Academic Medical Centers↗
PubMed1994

Coronary artery surgery in women compared with men: analysis of coronary risk factors and in-hospital mortality in a single centre.

OBJECTIVE: To determine differences in coronary risk factors between women and men and their relation to in-hospital mortality associated with coronary artery bypass grafting. DESIGN: Prospective observational study. SETTING: A regional cardiothoracic centre. PATIENTS: 482 (362 (75%) men and 120 (25%) women) consecutive patients who had primary isolated coronary artery bypass grafting. RESULTS: The women were on average three years older than the men (63 v 60 years, P < 0.001). Women more frequently had hypertension (47% v 33%, P < 0.01), diabetes mellitus (21% v 10%, P < 0.005), hypothyroidism (9% v 2%, P < 0.003), and a family history of premature coronary heart disease (49% v 31%, P < 0.0006). More of the men were cigarette smokers (67% v 45%, P > 0.00001). Many of the women and men had dyslipidaemia. Postmenopausal women had a higher concentration of serum total cholesterol than men of a comparable age, (7.3 mmol/l v 6.5 mmol/l, P = 0.0002). Although arterial grafts were often used in both sexes, they were more often used in men than in women (91% v 78% respectively, P = 0.0003). In-hospital mortality was 2.1% (1.4% in men and 4.2% in women, P = 0.14). The estimated one year probability of survival in men who had survived 30 days was 0.99 with 95% confidence interval 0.98 to approximately 1 while that for women was 0.97 with 95% confidence interval 0.91 to approximately 1. Univariate analysis showed that preoperative history of diabetes mellitus was a predictor of mortality (P = 0.03). CONCLUSION: There were differences in the incidence and type of risk factors in men and women who had coronary artery bypass grafting. Preoperative diabetes mellitus was a predictor of in-hospital mortality.

Age Distribution↗
PubMed1994

Hemodynamic and metabolic effects of paced linkage following heterotopic cardiac transplantation.

BACKGROUND AND PURPOSE: Heterotopic cardiac transplantation is a valuable surgical technique that maximizes the use of donor organs. However, recipient heart function may decline steadily postoperatively with resulting clinical deterioration. Paced linkage has the potential of reducing afterload and enhancing coronary flow of both hearts, thereby improving recipient- and donor-heart function. This may have long-term as well as short-term benefits. METHODS AND RESULTS: The study was performed on 11 heterotopic transplant recipients. The two hearts were linked with a pacemaker (paced linkage) to produce recipient heart systole during different periods of donor-heart diastole. The recipient ventricular contraction was timed to occur during early, mid, and late diastole of the donor heart. Hemodynamic baseline measurements were compared with the optimal counterpulsated data. Paced linkage produced significant improvements in total cardiac output, 5.0 +/- 0.9 compared with baseline 4.5 +/- 0.8 L/min (P = .021); recipient coronary sinus flow, 278 +/- 145 versus 186 +/- 108 mL/min (P = .022); and aortic systolic pressure, 135 +/- 27 versus 123 +/- 27 mm Hg (P = .005). There was an overall improvement in systolic ventricular performance in the recipient heart when pace linked, as evidenced by a significant increase in left ventricular systolic pressure of 118 +/- 36 compared with the baseline value of 108 +/- 33 mm Hg (P = .016), an increase in ejection period from 174 +/- 30 versus 203 +/- 48 (P = .046), and a decrease in the pre-ejection period of 147 +/- 37 when paced versus 181 +/- 39 milliseconds (P = .013). The metabolic studies showed a significant decrease in hypoxanthine release from a baseline level of 0.4 mumol/L to a paced value of -0.06 mumol/L (P = .002); these very low values would suggest that there is no evidence of ischemia. Hemodynamic changes in the donor heart included a significant reduction in the left ventricular end-diastolic pressure from 6.8 +/- 4.4 versus baseline of 10.5 +/- 5.8 mm Hg (P = .029) and in maximum -dP/dT from 3.2 +/- 1.7 versus baseline of 2.1 +/- 1.1. CONCLUSIONS: Paced linkage after heterotopic cardiac transplant produces significant functional improvements in both hearts. Permanent pacemaker implantation may sustain these acute benefits and prevent the premature deterioration of the recipient heart.

Adult↗
PubMed1993

Chordoma and chondroid neoplasms of the spheno-occiput. An immunohistochemical study of 41 cases with prognostic and nosologic implications.

BACKGROUND: Chordomas are rare neoplasms that show a proclivity for the spheno-occiput and sacral regions. A "chondroid" variant involving the spheno-occiput has been associated with improved survival. "Classic" or nonchondroid chordomas are uniformly immunoreactive for keratins. Chondroid chordomas are said to be immunonegative for epithelial markers, a feature used to support the concept that they represent chondrosarcomas. METHODS: The authors performed immunohistochemical studies on 25 patients with chondroid chordoma (mean age, 40.0 years) and on 16 patients with classic chordomas (mean age, 44.2 years) to establish tumor subsets based upon immunophenotype, specifically reactivity for epithelial markers. Kaplan-Meier survival curves were then constructed for each group with age as an added variable. RESULTS: All classic chordomas reacted for keratins as did 8 (32%) of the 25 chondroid chordomas. Forty-four percent of classic and 85% of chondroid chordomas were positive for S-100 protein. At 5 years, all patients younger than 40 years of age were alive in both the classic and chondroid groups. In contrast, of patients older than 40 years of age, only 22% with classic chordomas and 38% with chondroid chordomas were alive. CONCLUSIONS: Regardless of tumor subtype, age is the single most important variable in determining survival; patients younger than 40 years of age do better than older patients. There are no significant survival differences between patients with cartilage-containing tumors that are keratin immunopositive ("true" chondroid chordoma) or negative (chondrosarcoma). Immunostaining for keratins is of no prognostic value in assessing chondroid lesions of the spheno-occiput.

Adult↗
PubMed1993

A method for quantitative recovery of DNA from plate lysates of bacteriophage lambda-derived clones.

A method is described for the purification of DNA from recombinant clones in lambda vectors. Plate lysates are used as the starting material, with the phage suspension being either loaded directly onto mini-cesium chloride two-step gradients or first subjected to precipitation with polyethylene glycol-8000 before application to the gradients. A single centrifugation step is used and the DNA is isolated from the harvested bacteriophage by incubation at room temperature with formamide followed by ethanol precipitation. The small-volume gradients were effective in isolating phage particles in the range of 1.0 to 12.5 x 10(11) pfu with quantitative recovery of approximately 7 micrograms DNA/10(11) pfu. The method was tested with a cDNA clone in lambda gt10 (as an example of a lambda-derived vector which gives a plate lysate with a high titer) and rat genomic fragments cloned into EMBL3A (for which the plate lysates are of low titer). For both vectors, the purified DNA appeared free of inhibitory contaminants as assessed by restriction endonuclease digestion and subcloning of fragments.

Bacteriophage lambda↗
PubMed1993

Cortical blindness and seizures possibly related to cisplatin, vinblastine, and bleomycin treatment of ovarian dysgerminoma.

Ovarian dysgerminoma is the most common ovarian malignancy in young women. Conservative treatment is indicated in the reproductive-age woman who wishes to preserve childbearing capacity. This case report describes a patient with ovarian dysgerminoma who underwent chemotherapy with a cisplatin-vinblastine-bleomycin regimen that resulted in serious toxic complications--including cortical blindness and seizures--that were transient in nature. Although current chemotherapy regimens have dramatically improved the overall survival of women with germ-cell tumors, there are toxic complications such as those demonstrated in this report, and toxicity must be balanced against presumed benefit.

Adult↗
PubMed1992

Maxepa versus bezafibrate in hyperlipidemic cardiac transplant recipients.

Accelerated coronary artery disease is the most serious obstacle to long-term survival in cardiac transplant recipients. Lipid abnormalities are found frequently in these patients, and there is growing evidence that even minimally increased levels of cholesterol and triglycerides contribute to the development of accelerated coronary artery disease. However, the optimal lipid-lowering therapy after cardiac transplantation has not been defined. In an open, randomized study, the efficacy and safety of bezafibrate (400 mg/day) and fish oil (Maxepa) (10 g/day) for 3 months were compared in 87 cardiac transplant recipients with serum total cholesterol > 6.5 or triglycerides > 2.8 mmol/liter, or both. After 1 month, bezafibrate reduced total cholesterol by 13%, low-density lipoprotein cholesterol by 20% and apolipoprotein B by 13%. It also increased apolipoprotein A1 and high-density lipoprotein cholesterol by 12 and 20%, respectively, and significantly reduced fibrinogen at 3 months. Maxepa had no significant effect on these variables, but was as effective as bezafibrate in reducing triglycerides (36 and 31%, respectively). Both drugs increased lipoprotein (a) to a similar extent, and bezafibrate significantly increased serum creatinine. These results suggest that bezafibrate has better lipid-, apolipoprotein- and hemostatic modifying properties than does Maxepa, but its potentially adverse effect on renal function needs further investigation.

Apolipoprotein A-I↗
PubMed1992

Antibodies to defined histone epitopes reveal variations in chromatin conformation and underacetylation of centric heterochromatin in human metaphase chromosomes.

Unfixed metaphase chromosome preparations from human lymphocyte cultures were immunofluorescently labelled using antibodies to defined histone epitopes. Both mouse monoclonal antibody HBC-7, raised against the N-terminal region of H2B, and rabbit serum R5/12, which recognizes H4 acetylated at Lys-12, gave non-uniform labelling patterns, whereas control antibodies against total histone fractions H4 and H1 produced homogeneous fluorescence. HBC-7 bound approximately uniformly to the bulk of the chromosomes, but the major heterochromatic domains of chromosomes 1, 9, 15, 16 and the Y showed significantly brighter fluorescence. Serum R5/12 indicated an overall reduction in acetylation of H4 in metaphase chromosomes compared with interphase nuclei, although some specific chromosomal locations had considerably elevated acetylation levels. Acetylation levels in the major heterochromatic domains appeared extremely low. To investigate further the differences noted in heterochromatin labelling, metaphases from cultures grown in the presence of various agents known to induce undercondensation of the major heterochromatic domains were similarly immunolabelled. Decondensed heterochromatin no longer exhibited higher than normal immunofluorescence levels with HBC-7. The higher resolution afforded by "stretching" the centromeric heterochromatin of chromosomes 1, 9 and 16 confirmed the low level of H4 acetylation in these domains. We consider the implications of these observations in relation to chromatin conformation and activity.

Acetylation↗
PubMed1992

The organisation of repetitive DNA sequences on human chromosomes with respect to the kinetochore analysed using a combination of oligonucleotide primers and CREST anticentromere serum.

The spatial relationship between the families of repetitive DNAs present at the centromeres of human chromosomes and the position of the kinetochore was examined by combining immunocytochemistry with the PRINS oligonucleotide primer extension technique. Heterochromatic domains were decondensed with 5'-azacytidine to facilitate this study. Using this approach our results clearly show that the alphoid DNA sequences are closely associated with the kinetochore of human chromosomes. Simple-sequence satellite DNAs occupy separate, non-overlapping domains within the centromere. These two major families are separated by a third, relatively low-copy repetitive DNA family, SAU-3A. Pulse-field gel electrophoresis was employed to analyse the centromeric domain of human chromosome no. 9 in more detail and the results although preliminary support the conclusions drawn from the immunocytochemistry/PRINS approach.

Antibodies, Antinuclear↗
PubMed1992

Dipyridamole vasodilator response after human orthotopic heart transplantation: quantification by oxygen-15-labeled water and positron emission tomography.

To assess coronary vasodilator reserve after orthotopic heart transplantation, regional myocardial perfusion was measured with oxygen-15-labeled water and dynamic positron emission tomography in 14 cardiac allograft recipients who were not experiencing rejection and who had no angiographic evidence of epicardial coronary sclerosis 15 to 73 months (mean +/- SD 43 +/- 19) after transplantation (group I). Twelve normal men with an average age of 31 years (group II) served as a control group. Regional perfusion was measured at rest and after the intravenous administration of 0.6 mg/kg body weight of dipyridamole. Rest regional myocardial blood flow was homogeneously distributed throughout the left ventricle and was significantly higher in transplant recipients (mean 1.16 +/- 0.26 ml/g per min [range 0.8 to 1.73] than in normal subjects (mean 0.85 +/- 0.13 ml/g per min [range 0.57 to 0.99]; p = 0.001) as was rest heart rate-systolic blood pressure product (rate-pressure product 11,255 +/- 2,540 vs. 7,073 +/- 1,306; p less than 0.001). After dipyridamole, perfusion in the transplant recipients was homogeneous and slightly lower (2.73 +/- 1.03 vs. 3.40 +/- 1.09 ml/g per min; p = NS), whereas rate-pressure product was slightly higher (12,179 +/- 2,266 vs. 10,885 +/- 1,895; p = NS) than the value in normal subjects. Dipyridamole vasodilator response (dipyridamole/rest myocardial blood flow) ranged from 1.23 to 4.92 (mean 2.50 +/- 1.13) in group I and from 2.65 to 5.45 (3.97 +/- 0.89) in group II (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

A stereological study of the human ovarian surface epithelium.

The surface of the ovary has been found to be composed of two types of epithelial cells called A and B cells which are found in their own respective zones, the A and B zones. A quantitative study was undertaken to determine the mean cell volumes and cell ultrastructure. Ovarian biopsies were taken from six women and A and B zones, having been identified by scanning electron microscopy, were re-embedded for transmission electron microscopy. Stereological measurements using point sampled intercepts were made on vertical sections and showed that B cells are significantly larger than A cells. The volume weighted mean cell volumes of the A and B cells were 237.3 microns 3 and 676.8 microns 3 respectively. The volume fractions of the nucleus and mitochondria were similar in the two cell types. Although the vesicle content of each type was similar, a large variation between cases made the interpretation difficult. The stereological tools used in this study proved to be easy and efficient estimators of surface cell ultrastructure and give an important direction for ultrastructural research.

Biopsy↗
PubMed1992

Definition of an advanced nursing practice role in the NICU: the clinical nurse specialist/neonatal practitioner.

We surveyed 655 health professionals affiliated with tertiary level neonatal intensive care units in Canada and the United States to define an expanded role for nurses in neonatology and to determine the educational requirements for the role. The role, comprising advanced clinical practice, educational, research, and administrative responsibilities, is a blend of nurse practitioner and clinical nurse specialist activities. Based on survey findings, a neonatal stream within the existing Master of Health Sciences program at McMaster University was developed. To date, 15 clinical nurse specialists/neonatal practitioners (CNS/NPs) are employed in five neonatal intensive care units in Ontario and other related institutions. A randomized trial to evaluate these individuals is in progress.

Humans↗
PubMed1992

Perforated peptic ulcer in the Hunter region: a review of 174 cases.

A review of 174 consecutive patients admitted with a diagnosis of perforated peptic ulcer to eight Hunter Region hospitals during 1979-86 is presented. Among the female admissions, the proportion of patients greater than 70 years of age was twice that in males. One-third of all perforations were in females who accounted for two-thirds of all perforated gastric ulcers. Multivariate analysis revealed that perforations located in the stomach and older age were both significant independent variables adversely affecting outcome following surgery. In contrast, shock at presentation and delay in operating were not statistically significant independent risk factors.

Adolescent↗
PubMed1992

Limited value of the resting electrocardiogram in assessing patients with recent onset chest pain: lessons from a chest pain clinic.

OBJECTIVE: To evaluate a clinic set up specifically to assess patients with recent onset chest pain, particularly those presenting with a normal resting electrocardiogram. DESIGN: Retrospective review of case notes. SETTING: Cardiac department of a tertiary referral cardiothoracic centre. PATIENTS: 250 consecutive patients with recent onset chest pain seen within 24 hours of general practitioner referral. OUTCOME MEASURES: Clinical diagnosis and management. RESULTS: 40% of patients were seen within seven days of the onset of symptoms. Twenty seven per cent had non-cardiac symptoms and could be discharged while 60% were considered to have cardiac pain. Sixty six patients (26%) were admitted directly from the clinic and 48 of these underwent coronary angiography within three weeks. Seventy patients (28%) have so far undergone intervention (angioplasty or coronary artery surgery), 22 within one month of presentation. One hundred and nine patients (44%) presented with a normal resting electrocardiogram, 21 of whom were considered to have unstable angina. Forty one of these patients were investigated of whom 37 were found to have significant coronary disease and 26 have undergone intervention. CONCLUSIONS: This experience highlights the inadequacy of a routine electrocardiogram reporting service in patients with recent onset of chest pain. An alternative facility offering immediate and complete cardiac assessment produced patient benefit with early diagnosis and intervention. Investigation of these patients, however, accounted for 5% of cardiac catheterisation laboratory throughput; this was a significant additional and unscheduled workload.

Adult↗
PubMed1992

Regional localization of the selenocysteine tRNA gene (TRSP) on human chromosome 19.

The human selenocysteine tRNA gene (TRSP) has been localized on chromosome 19q13.2-->q13.3 by in situ hybridization and ordered with respect to other genes and anonymous DNA markers in this region by linkage analysis in the forty CEPH pedigrees. These loci span only 10 cM in males and about 30 cM in females. The order of the loci is cen ... D19S7-D19S9-D19S47-CYP2A-CYP2F1-APOC2++ +-(TRSP, CKM). CYP2B flanks the CYP2A and CYP2F1 loci, but it cannot be determined whether it is proximal or distal to the other two cytochrome P450 loci with respect to the centromere.

Chromosome Banding↗
PubMed1991

The regulation of hepatic lipase and cholesteryl ester transfer protein activity in the cholesterol fed rabbit.

Hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) activities are both increased in the rabbit by cholesterol feeding. The in vivo regulation of HL and CETP were explored by examining changes in specific steady-state mRNA levels upon cholesterol feeding. On feeding rabbits cholesterol, HL activity increased 3-fold after 2 days and remained at 2.6-times the control value at 28 days. Specific rabbit HL mRNA levels were assessed by dot blot analysis of liver poly (A)+ RNA hybridized with the human HL cDNA. No significant changes in liver HL mRNA accompanied the increase in activity seen at days 2 and 7. At day 28 a modest rise of 46% was observed. A significant rise in CETP activity, evident 7 days after the commencement of cholesterol feeding, was maintained until day 28 when it was 2.4-times the control value. Using the human CETP cDNA as probe, rabbit liver CETP mRNA was also found to increase by day 7, rising to 3.7-times control by day 28. The strong temporal relationship between the rise in CETP activity and mRNA (r = 0.55, P = 0.02) suggests that the regulation of CETP may be primarily effected by the levels of specific mRNA. In contrast, the discordance between levels of lipase activity and mRNA suggests that post-transcriptional events may be more important in the regulation of HL in the cholesterol fed rabbit.

Animals↗