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Biomedical subjects

R Stewart

Publications and source records attributed to R Stewart.

At least 163 records · Page 9Linked to original sources

Cortical rotation of the Xenopus egg: consequences for the anteroposterior pattern of embryonic dorsal development.

We first review cortical-cytoplasmic rotation, a microtubule-mediated process by which the Xenopus egg, like other amphibian eggs, transforms its polarized cylindrical symmetry into bilateral symmetry within the first cell cycle after fertilization. This transformation, the earliest of many steps leading to dorsal development, involves the displacement of the egg's cortex relative to its cytoplasmic core by 30 degrees in an animal-vegetal direction. As rotation is progressively reduced by microtubule-depolymerizing agents, embryos develop with body axes progressively deleted for dorsal structures at the anterior end. With no rotation, ventralized embryos are formed. In an effort to comprehend this progressive effect on embryonic organization, we go on to review subsequent developmental process depending on rotation, and we propose, with evidence, that reduced rotation leads to a reduced number of vegetal dorsalizing cells, which induce during the blastula stage a Spemann organizer region of smaller than normal size. The reduced organizer then promotes a reduced amount of cell rearrangement (morphogenesis) at gastrulation. Reduced morphogenesis seems the proximate cause of the incompleteness of axial pattern, as shown further by the fact that embryos that are normal until the gastrula stage, if exposed to inhibitors of morphogenesis, develop body axes that are progressively less complete in their anterior dorsal organization the earlier their gastrulation had been blocked. We discuss why axial pattern might depend systematically on morphogenesis.

Animals↗

Ebstein's anomaly: natural and unnatural history.

Clinical features and natural history were analyzed in 30 patients with Ebstein's anomaly (mean age 26 years, range 1.5-58 years, 53% females). The main presenting symptoms were dyspnea and fatigue (83%). At presentation, there were six patients (20%) in New York Heart Association Functional Class (NYHAFC) I, nine (30%) in NYHA-FC II, and 15 (50%) in NYHA-FC III or IV; 12 patients (40%) were cyanotic. Common auscultatory findings were widely split second heart sound in 21 (70%), third heart sound in 14 (47%), fourth heart sound in 16 (53%), and a systolic murmur in 22 (73%). Right bundle branch block was present in 21 (70%), documented supraventricular tachycardia in seven (23%), and Wolff-Parkinson-White syndrome in three (10%). Catheterization was performed in 93% without complications. Fourteen patients were treated surgically (12 [86%] in NYHA-FC III or IV, 10 [71%] with associated anomalies); tricuspid valve replacement was performed in eight, atrial septal defect repair in two, accessory pathway ablation in two, right atrial plication in one, and automatic cardioverter defibrillator implantation in one. Surgical treatment improved 10 patients from NYHA-FC III or IV to NYHA-FC I or II. Death occurred in nine patients (five treated surgically and four medically); four of these deaths were sudden. In the eight patients who had tricuspid valve replacement, there were one operative and two late deaths. The authors conclude that surgical therapy with tricuspid valve replacement improves the clinical status of patients who are severely ill. Risk of sudden death remains an important problem in patients with Ebstein's anomaly regardless of severity of the disease and mode of treatment.

Adolescent↗

Critical cardiac transport: air versus ground?

The helicopter transport of acute cardiac patients has become increasingly common, although no study has examined solely the effect of such transport on outcome in this subset of patients. A combined air and ground critical care transport service provided the opportunity for a direct comparison of patients with acute cardiac conditions (myocardial infarction or unstable angina) transported either by our helicopter or by a specially equipped critical care ground vehicle. Both air and ground components were similarly equipped in terms of personnel and medical equipment. Seventy-eight (27 ground, 51 air) transport cases were studied. Both patient groups were comparable in terms of age, sex, Killip classification, and diagnosis. Serious untoward events, defined as arrhythmias, chest pain, hypotension, bradycardia, seizures, and cardiac arrest, occurred in 41% of air transports and 7.5% of ground transports (P less than .002). The overall incidence of untoward events was also significantly greater with air transports (25/51, or 49%) than with the ground vehicle (4/27, or 15%; P less than .005). The reasons for these differences are unknown.

Aged↗

Delayed improvement in exercise capacity after cardioversion of atrial fibrillation to sinus rhythm.

In some patients symptoms improve after the restoration of sinus rhythm from atrial fibrillation. To assess the size and mechanism of such change, exercise capacity and pulsed Doppler left ventricular inflow velocities were assessed in 20 patients with established atrial fibrillation. Treadmill exercise capacity was assessed by measuring maximal oxygen consumption and anaerobic threshold before and on day 1 and 28 days after elective DC cardioversion. The relative contribution of atrial contraction to left ventricular filling was determined by relating the maximum height of the A wave to the maximum height of the E wave (A/E) of the Doppler velocity time curve. Cardioversion was successful in 14 patients. Maximal oxygen consumption and anaerobic threshold were unchanged on day 1 and increased by day 28 in all 14 patients. The percentage improvement was inversely related to the baseline values; however, the absolute improvement was small in all patients. The mean A/E ratio increased significantly from day 1 to day 28 in all 14 patients. Thus the restoration of sinus rhythm was associated with a delayed improvement in exercise capacity that may in part be due to a slow improvement in atrial contractility and peak cardiac output after cardioversion.

Aged↗

Griffiths in theory and practice: a research assessment.

This paper focuses upon one of the major recommendations of the Griffiths Report: the appointment of general managers at each level in the NHS. It is based on a study of a sample of 20 district general managers (DGMs) who had been followed for a year to 18 months at the time this paper was written. Their first major task was to restructure their districts; some of the variations in these structures are described, together with what happened to officers from different professional backgrounds, and the reactions of the doctors, nurses, and paramedics. The ways in which the DGMs sought to change the culture of the NHS are outline. A number of major ongoing dilemmas are identified. The study suggests what the learning needs are of present and future general managers.

Administrative Personnel↗

Cyclosporin-associated microfibrils in cardiac transplant patients.

Endomyocardial biopsies from 21 cyclosporin-treated cardiac transplant patients were studied at the ultrastructural level. Eight patients exhibited focal interstitial accumulation of filaments, which most commonly measured 8-10 nm in diameter (range 7-16 nm). The filaments were straight, hollow, and nonbranching. Filament accumulation was observed as early as 4 days posttransplant. No filament accumulation was observed in 17 donor endomyocardial biopsies obtained at the time of transplantation. The ultrastructure of the filaments was similar to that of amyloid fibrils. Stains for amyloid at the light microscopic level were uniformly negative, however. Until the exact nature of the filaments is determined, we propose that they be referred to as cyclosporin associated microfibrils.

Actin Cytoskeleton↗

Natural killer cells in the host response to melanoma.

Using an immunoperoxidase technique, we have investigated natural killer (NK) cells in the host response to malignant melanomas and melanocytic nevi in frozen sections. Eight primary melanomas, 12 metastatic melanomas, and 31 dysplastic nevi were studied. NK cells were identified phenotypically using an antibody, B73.1, against an Fc receptor present only on NK cells and neutrophils. Rare NK cells were identified in three of 31 dysplastic nevi and in one of eight melanomas. In contrast, significant numbers of NK cells were identified in ten of 12 metastases.

Humans↗

Characterization of anti-cerebroside sulfate antisera using a theoretical model to analyse liposome immune lysis data.

Antisera to the acidic glycolipid cerebroside sulfate (sulfogalactosyl ceramide) were raised in rabbits by several different methods. Reactivity with cerebroside sulfate was detected from complement-mediated lysis of liposomes composed of phosphatidylcholine/cholesterol/cerebroside sulfate and containing the spin label tempocholine chloride as a marker substance. Both cholesterol rich particles and lipid bilayer liposomes containing phosphatidylcholine and cholesterol were effective carriers for cerebroside sulfate, in combination with methylated bovine serum albumin for intravenous immunization, and with Freunds complete adjuvant for subcutaneous immunization. The antisera raised by the different methods were characterized with respect to their cross reactivity with other lipids and the relative concn of specific antibodies and their affinities for cerebroside sulfate using a theoretical model developed earlier [Vistnes A. I. (1984) J. Immun. Meth. 68, 251] for analysis of data from immune lysis of liposomes. Differences in these properties, both of which can affect antibody titer, could be detected for antisera raised by different methods and obtained at different times after immunization. Some of the antisera also reacted non-specifically to varying degrees with other anionic lipids indicating that the anti-cerebroside sulfate antibodies could bind non-specifically to anionic lipids by electrostatic interactions. This suggested that basic amino acid residues may be an important part of the antibody receptor binding site for the glycolipid head group. An important implication of this result is that antibodies raised against anionic glycolipids should be tested for non-specific binding to anionic phospholipids.

Animals↗

Does indirect consultation lead to overprescribing in general practice?

Indirect consultations (by telephone or receptionist) are of increasing importance in general practice and may result in more prescribing than during direct (face to face)-consultations. We analysed prescribing data for 14,660 disorders, presented in one week in 52 general practices. In general, a significant, but hardly relevant increase in prescribing during indirect consultations was observed. The effect varies strongly for different disorders and was especially relevant for repeat-prescriptions for the following conditions: musculoskeletal- and connective tissue diseases, endocrine, nutritional and metabolic disorders and disorders of the female genital tract.

Drug Prescriptions↗

Prostaglandins, leukotrienes, and other arachidonic acid metabolites in nasal polyps and nasal mucosa.

Prostaglandins (PGs) and leukotrienes (LTs) are known to play an important role in allergic inflammatory reactions. The triad of aspirin sensitivity, nasal polyposis, and asthma led us to suspect that PGs, LTs and other arachidonic acid metabolites may be involved in the pathogenesis of nasal polyps. The purpose of this study was to determine arachidonic acid metabolites and to measure concentrations of PGs and LTs in nasal polyps and nasal mucosa. Samples of nasal polyps and nasal mucosa were obtained at the time of polypectomies and nasal procedures. Metabolites of arachidonic acid in tissue were determined by incubation of tissue-homogenates with 14C-arachidonic acid and analyses with thin-layer chromatography and high performance liquid chromatography (HPLC). Levels of PGE2, 6-keto-PGF1 alpha, thromboxane (Tx)B2, 15-hydroxyeicosatetraenoic acid (HETE), LTC4, LTB4 were measured by radioimmunoassay. The predominant arachidonic acid metabolite in both nasal polyps and mucosa with 15-HETE. The HPLC analysis showed that the predominant metabolite in nasal polyp was 15-HETE, especially in polyps from aspirin sensitive patients. Levels of 15-HETE and PGE2 were higher in polyps from patients with a history of allergy than from nonallergic patients. Levels of LTC4 and LTB4 in nasal polyps were determined. The findings of this study will help to explain biochemical basis of the pathogenesis of aspirin-sensitive nasal polyps and to develop better medical treatment for them.

6-Ketoprostaglandin F1 alpha↗

Effects of beta-aminopropionitrile after glaucoma filtration surgery: pilot human trial.

Beta-aminopropionitrile fumarate, an inhibitor of collagen cross-linking, was used topically in patients after filtration surgery for difficult cases of glaucoma (aphakic, repeat surgery, neovascular). Twenty-three patients received the drug for a total treatment period of three months following surgery. The mean preoperative intraocular pressure was 40.0 +/- 14.1 mm Hg (mean +/- standard deviation). The mean postoperative pressure was 19.0 +/- 8.9 mm Hg, with the mean follow-up at 26.4 +/- 11 weeks. The overall success rate was 74%, with success being defined as an intraocular pressure of 22 mm Hg or less at the last visit. Side effects consisted primarily of stinging immediately after the medication was applied. Inhibition of collagen cross-linking may represent an alternative method to the use of injectable 5-fluorouracil to maintain patency of filtration blebs.

Administration, Topical↗

Reversibility of myocyte injury in moderate and severe acute rejection in cyclosporine-treated cardiac transplant patients.

Myocyte injury in acute cardiac transplant rejection was studied ultrastructurally in 45 patients. Mild myocyte injury consisted of increased glycogen granules and mitochondria, and condensation and streaming of myofilaments. More severe cell injury was characterized by clumping of Z-band material at the periphery of the cell and loss of sarcomeric units. Cell swelling was not seen, and intramitochondrial dense deposits (indicative of irreversible cell injury) were rarely seen. Restoration of normal myocyte ultrastructure occurred after treatment for rejection. Although the light microscopic appearance of moderate or severe acute rejection may suggest myocyte necrosis, this is rarely observed ultrastructurally. We conclude that the majority of cell injury in acute rejection is potentially reversible.

Biopsy↗