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Biomedical subjects

A Mitchell

Publications and source records attributed to A Mitchell.

At least 163 records · Page 9Linked to original sources

Determination of the test performance of less costly methods of Helicobacter pylori detection.

Since Helicobacter pylori (Hp) has become so important in the management of peptic ulcers, it is imperative that noninvasive and inexpensive methods of diagnosis be available. The objective of this prospective, double-blind study was to determine the performance of the noninvasive 14C-urea breath test and the less expensive hematoxylin-phloxin-saffron (HPS) and Giemsa stains in the detection of this infection. As well, we set out to determine the minimal number of biopsies required to make an accurate diagnosis. Fifty consenting adults referred for gastroscopy underwent antral biopsies for HPS, Giemsa and Steiner silver staining and a 14C-urea breath test. The ability of HPS, Giemsa, and the breath test to differentiate between the presence or absence of Hp infection as defined by the silver stain was assessed using contingency table analysis. Hp was detected in 24 patients with the silver stain. Half of these patients had evidence of ulcer disease, compared to 3 of 26 patients who were negative for Hp on silver stain (p < 0.01). The Hp positive group were more frequently male (62% vs. 31%, p < 0.05) and more often had chronic active gastritis (96% vs. 7.7%, p < 0.001). The sensitivity of the breath test, HPS, and Giemsa stains were 95.8% (95% confidence interval: 79-100%), 75% (53-90%), and 95.8% (79-100%), respectively. Specificity was 100% (87-100%) for all 3 methods of detection. The breath test was also able to discriminate between heavily infected and moderately infected patients as defined by silver stain (p < 0.05), and could be shortened from 30 to 15 min without any loss of accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Experience of an implantable central venous access system in a district general hospital.

Reliable access to a central vein is increasingly important in the treatment of major acute and chronic disease. The use of an implantable central venous access device in a district general hospital is reviewed. Fifty-four PortaCaths (Kabi Pharmacia, Milton Keynes, UK) were inserted in 51 patients over a 7-year period. Most patients had haematological disease, often with neutropenia and thrombocytopenia. There were a total of 22,515 catheter days experience. Twelve catheters were removed for complications with an overall complication rate of 0.93/1000 catheter days. There were four line infections and four episodes of periport sepsis. Occasional catheter thrombosis was usually cleared with urokinase. Neutropenic and immunocompromised patients had an increased complication rate. PortaCaths were well tolerated by patients and required minimum maintenance. An implantable central venous access device proved safe and reliable for use in a district general hospital.

Adolescent↗

Secretion of biologically active human proapolipoprotein A-I in a baculovirus-insect cell system: protection from degradation by protease inhibitors.

Studies of the structure and function of apolipoprotein A-I (apoA-I) often require its purification by delipidation of high density lipoprotein isolated from large quantities of human plasma and separation of apoA-I from other plasma apolipoproteins. To reduce the need for extensive purification procedures, we have developed an insect cell/baculovirus expression system for the production and secretion of human proapoA-I. The recombinant baculovirus containing full-length human apoA-I cDNA, when introduced into Spodoptera frugiperda, directs the synthesis of preproapoA-I, which is subsequently secreted into the growth medium as proapoA-I, indicating correct processing of the signal peptide during secretion. To prevent the extensive degradation of secreted proapoA-I, leupeptin and pepstatin A were added to the serum free cell culture medium. The protein was simply purified by filtration of the medium, which contained up to 80 mg/l proapoA-I, followed by chromatography on phenyl-sepharose CL-4B. The resultant proapoA-I was found to bind lipid and to activate lecithin:cholesterol acyltransferase as effectively as apoA-I from human plasma. The advantage of this expression system is the ease of purification of intact, biologically active apoA-I in high yield.

Animals↗

Activin signalling and response to a morphogen gradient.

Using combinations of amphibian embryo tissues, it is shown that the selection of genes expressed by a cell is determined by its distance from a source of activin, a peptide growth factor contained in vegetal cells and able to induce other cells to form mesoderm. This long-range signal spreads over at least 10 cell diameters in a few hours. It does so by passive diffusion, because it can by-pass cells that do not themselves respond to the signal nor synthesize protein. These results provide direct support for the operation of a morphogen concentration gradient in vertebrate development.

Activins↗

A randomized pilot trial of low-dose combination lipid-lowering therapy following coronary artery bypass grafting.

Vein graft atherosclerosis is a common and serious complication of coronary artery bypass grafting (CABG). There is mounting evidence that lipoprotein abnormalities play an equally important role in the development of lesions in saphenous vein grafts after CABG as in native coronary vessel disease. The potential benefit of low-dose lipid lowering combination therapy in these patients has not been investigated. In a randomized, double-blind, placebo-controlled study, we compared the efficacy and safety of a low-dose combination of colestipol 10 g and simvastatin 10 mg/day (CS) to colestipol 10 mg and bezafibrate 400 mg/day (CB) for 2 months in 33 patients with serum total cholesterol > 6.5 mmol/l and triglyceride < 4.5 mmol/l who had undergone CABG for severe coronary artery disease. In the CS group, total cholesterol decreased by 29% and low-density lipoprotein (LDL) cholesterol by 42%; similarly, CB reduced total cholesterol by 17%, LDL cholesterol by 23%, triglyceride by 19%, and increased high-density lipoprotein (HDL) cholesterol by 14%. Lipoprotein (a) and hemostatic factors were unaffected by either therapy in this study. Both combination therapies were well tolerated with no significant clinical or biochemical side effects. We conclude that low-dose combinations of colestipol and simvastatin or colestipol and bezafibrate are effective and well tolerated in the management of moderate hyperlipidemia in patients who had undergone CABG.

Analysis of Variance↗

Postoperative hemodynamic improvement with paced linkage of the donor and recipient hearts following heterotopic cardiac transplantation.

It has been shown that following heterotopic heart transplantation the recipient left ventricle ejects more effectively when it contracts out of phase with the donor left ventricle. However, this is rarely the situation, as the two hearts beat independently of one another and the denervated donor heart tends to beat faster than the recipient. In this study the hemodynamic effects of connecting the two hearts by an external temporary dual-chamber pacemaker were evaluated. The donor right ventricle was sensed and the recipient right atrium paced after a timed delay. The delay was adjusted so that recipient systole coincided with donor diastole. Eleven patients were studied in the first postoperative day. Pacing resulted in an improvement in cardiac output from 5.0 to 5.6 l/min (p = 0.003) and a reduction in pulmonary capillary wedge pressure from 16 to 12 mmHg (p = 0.0035). This was associated with a 35% reduction in inotrope requirements. It is concluded that sequential pacing of the two hearts is a useful adjunct to inotropic support in the postoperative period.

Cardiac Output↗

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↗

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↗

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↗

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↗

The use of unstented homograft valves for aortic valve reoperations. Review of a twenty-three-year experience.

Unstented homograft valves offer several theoretical advantages when used for patients who have had previous operations on the aortic valve. Between January 1970 and February 1993, 177 patients received unstented homograft valves after previous aortic valve operations. One hundred thirty-four patients had previous aortic valve replacement in the form of homografts (101 patients), mechanical prostheses (24 patients), and bioprostheses (9 patients), and 43 had previous valve repair. The indication for reoperation was deterioration of a noninfected valve (124 patients), infective endocarditis (40 patients), and failure of a noninfected mechanical valve (12 patients). Fresh homograft valves were implanted in 60 patients, homografts preserved in antibiotics were used in 111 patients, and 6 patients received cryopreserved valves. Aortic valve and root replacement was performed in 60 patients, and in 117 the homograft was inserted freehand in the subcoronary position. The early mortality was 5.1%. The actuarial survival at 10 years was 71%. Multivariate analysis demonstrated that patients with previous homograft replacement have a better long-term survival than patients who had previous mechanical valves (p = 0.017). The freedom from valve-related death and reoperation was 70% at 10 years. Fresh homografts faired better than antibiotic-sterilized homografts (p = 0.007). None of the patients had recurrence of endocarditis at 6 months, although 1 patient died of uncontrolled infection despite valve replacement. The freedom from recurrent endocarditis was 88% at 10 years. We conclude that unstented aortic homografts provide good early and long-term results for aortic valve reoperations, particularly in patients with previous homograft replacement. Recurrent endocarditis is uncommon even in patients operated on for prosthetic valve infections.

Adolescent↗

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↗

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↗