Oncocytic cancers of the thyroid. Hürthle cell cancers

Nonvalvular atrial fibrillation is a frequent finding in elderly patients; the risk of thromboembolic complications is comparable to that reported in patients with rheumatic atrial fibrillation. Recently, 6 multicenter clinical trials (5 primary prevention, 1 secondary prevention trail) have been published which demonstrate equivocally that oral anticoagulation therapy significantly reduces the embolic risk in patients with nonvalvular atrial fibrillation by about 67% to 87%. The target INR of anticoagulation with warfarin in 2 of these trials was 1.4 to 2.8 ("low-dose" warfarin); interestingly, the magnitude of risk reduction was similar to these 2 studies with "low-dose" warfarin as it has been reported by the others using full-dose warfarin with an INR target between 2.0 and 4.5. Side effects of oral anticoagulation (severe bleeding complications) were low in these trials. Thus, the benefit-risk ratio in these 6 clinical trials encourage the use of oral anticoagulation in patients with nonvalvular atrial fibrillation. It will be a challenge to transfer these results to clinical practice, and to define in more detail the risk-benefit ratios for subgroups of patients with atrial fibrillation, e.g. patients > 75 years of age, or patients with "lone" or paroxysmal atrial fibrillation. It is well established that patients with chronic atrial fibrillation undergoing medical or DC-cardioversion are at risk for thromboembolic complications. In previous studies, this risk appears to be in the range of 2% without concomitant anticoagulation, but only 0.33% in those patients with concomitant anticoagulation. Thus, it is widely accepted that patients should be anticoagulated for at least 2 weeks prior and after planned cardioversion. Recently, an alternative concept has been proposed omitting anticoagulation before cardioversion; instead, transesophageal echocardiography is used to exclude intracardiac thrombi. Because it is known that mechanical function of the left atrium and appendage is still impaired after cardioversion, this concept of echocardiographic-guided cardioversion does not assign the necessity of anticoagulation at the day of cardioversion, and 2 weeks afterwards. The safety aspects of this concept of echocardiographic-guided cardioversion is under current investigation.     

Optimized galenics improve in vitro gene transfer with cationic molecules up to 1000-fold

Reproducible and optimized complex formation between polyanionic DNA and a polycationic vector is a key aspect of nonviral gene transfer systems. To this end, several factors relevant to in vivo delivery have been tested repeatedly on several cell types. Gene transfer with a lipopolyamine (transfectam) in the presence of serum was increased over 10-fold by sequential addition of the lipid to DNA. Paradoxically, high complex concentrations (> 200 micrograms DNA/ml) led to large enhancements too, which points to the fact that formation of productive complexes is a slow process. Each parameter, more than compensates for the decreased efficiency generally observed with nonviral vectors in serum. Transfectam and PEI (polyethylenimine)-mediated transfection also improved after mild centrifugation of the complexes on to the cells. These individual factors were shown to be essentially multiplicative, leading altogether to approximately a 1000-fold transfection increase with a luciferase reporter gene. Finally, 25 cell lines and primary cells (including fibroblasts, hepatocytes and endothelial cells) were successfully transfected over a five orders-of-magnitude efficiency range, From this large set of data, a general relation between the overall transfection level (as measured by luciferase reporter gene expression) and the fraction of transfected cells (histochemically stained for beta-galactosidase) could be inferred. Finally, transfectam and PEI displayed similar trends over this large range of efficiencies, which reinforces the hypothesis of a common transfection mechanism where the key endosome-releasing stop occurs through a "proton sponge' effect.     

Therapeutic strategies in acute myocardial infarction. Results of STIM 93 registry

A registry was set up by the national college of cardiologists practicing in general hospitals in February 1993. The data concerned mode of admission, demographic details, initial clinical and haemodynamic evaluation and hospital outcome. Special attention was given to the electrocardiographic changes before and, in patients receiving thrombolytic therapy, after treatment. An analysis of predictive factors for mortality was performed both in the group of patients "revascularised" and in the group treated conventionally. One thousand and twenty three cases from 327 centres were analysed. There were 1292 men and 531 women, with an average age of 67.9 years. The average time interval from onset of symptoms to hospital admission was 5 h 30 min, 56.8% of patients arriving within 6 hours. 36.4% of the population underwent thrombolysis or angioplasty, 75% of patients under 75 years of age admitted before the 5th hours underwent a procedure of myocardial revascularisation. The hospital mortality was 14%, 8.7% in those revascularised and 17% in patients treated conventionally. Factors predictive of mortality were age, female gender, Killip Classes III or IV, systolic blood pressure of less than 100 mmHg, heart rate of more than 100/min and contraindications of thrombolysis. The maximum ST depression, the sum of ST depression, the sum of ST elevation and depression, were also significant predictive factors of a fatal hospital outcome in the whole population group and in patients treated conventionally. In the reperfused group, only the initial sum of ST elevation and depression was predictive of mortality: 120 minutes after the beginning of thrombolysis, the sum of ST elevations and of elevations and depressions was predictive of twice the mortality when the values exceeded 0.6 mv and 1.4 mv respectively.     

Clinical, morphologic and immunophenotypic data based on 10 cases of canine muco-cutaneous epidermotropic T-lymphoma (analogous to Mycosis Funcgo?de). Important of an animal model of spontaneous pathology

Our serie of ten canine cutaneous epitheliotropic T-cell lymphomas (CTCL), is found in old dogs, belonging mainly to the Boxer breed. Site on the mucous membranes (especially buccal), the muco-cutaneous junctions, their clinical expression is polymorphous. Lesions, follow on one after another (erythema, plaques, nodules) and are diversely associated in a given animal, the borders between the different stages often being difficult to establish. Adenopathies noted at the time of the diagnosis or during the course of the condition are accompanied by an involvement of the blood and organs (analogous to Sézary's disease). The progression of the disease can be very rapid in the buccal forms, which are generally aggressive, and in cases of violent, uncontrollable pruritus, which may be disturbing for the owner (with requests for euthanasia). The neoplastic infiltrate is constituted of small lymphocytes with hyperchromatic, convoluted nuclei (incipient stages), then large cells with a "histiocytic" appearance for the nodules. Epitheliotropism, which is maximal for the infiltrated plaque stage, shows up either in the form of a flux of totally epitheliotropic isolated cells (Ketron-Goodman type) or in that of Pautrier abscess-like collections. THe veterinary literature is in agreement that the CTCL cell expresses CD3, but two recent studies are in contradiction as regards its membership of helper or cytotoxic/suppressor populations. For our 10 cases, all the cells of lymphocytic morphology were, without exception, CD3+ and CD45+, irrespective of their situation within the epithelium or the chorion. The CD3+ cells in the epithelium were systematically CD8+, CD4- (confirming P.F. Moore's observations), expressing CD5 in a variable way, and, mostly, the Ki-67 nuclear proliferation Ag. The CD3+ cells of the chorion were exclusively, or mainly, CD8+, and occasionally CD4+. They expressed CD5 in a variable way, and, for a minority, the Ki-67 nuclear proliferation Ag. On the pathogenic level, it may be suggested that a T clone, CD8+, undergoes the "homing" phenomenon within the epithelium, enters the cell cycle, then manifests a tropism towards the chorion, which it infiltrates. Despite some particularities, which may be clinical (serious mucous attacks), cytological (the "histiocytic" appearance of the nodule cells) or immunophenotypic (expression of CD8, similar to what is observed in man in a considerable number of Pagetoid reticulosis), CTCL constitutes an interesting model of spontaneous pathology, and could prove useful in: - identifying various etiological factors (given that the dog, as a close commensal of man, is subject to the same environmental factors).     

Supramalleolar osteotomy for ankle valgus in myelomeningocele

Oral fibroblasts stimulated invasion of oral-carcinoma cells into the collagen matrix. The mechanisms of the fibroblast-induced stimulation of invasiveness was further investigated by examining cell motility and proteolytic activity of tumor cells, using mainly an adenoid-cystic-carcinoma cell line (ACCS) and normal fibroblasts from gingival tissues. Conditioned medium from the fibroblasts grown in serum-free medium was fractionated on a Superdex 200 pg column, and Peak 1 eluted at 200 to 300 kDa and Peak 2 eluted at 50 to 100 kDa were found to contain different specific activity. Treatment of ACCS cells with Peak 1 resulted in an increase in the production of proteolytic enzymes. Peak 2 stimulated both chemotaxis and chemokinesis of ACCS cells. A chemotactic factor was purified from the heparin-unbound fraction of Peak 2 by anion exchange and hydrophobic chromatography, and was named "fibroblast-derived motility factor (FDMF)". At 1 microg/ml, FDMF stimulated chemotaxis of ACCS cells by 4-fold compared with unstimulated controls. Characterization of the physicochemical properties of FDMF suggested that it might be different from any known motility factors. Exposure of ACCS cells to FDMF resulted in reduced amounts of actin stress fiber in the cytoplasm and induction of tyrosine phosphorylation of several cellular proteins detectable 30 to 60 min after treatment. These FDMF-induced changes were blocked by pre-treatment either with genistein or with pertussis toxin. These findings suggest that FDMF may be a novel protein which stimulates cell motility via a signaling pathway mediated by a pertussis-toxin-sensitive G protein and tyrosine phosphorylation.     

Effect of reduced dietary sodium on blood pressure: a meta-analysis of randomized controlled trials

OBJECTIVE:- To ascertain whether restriction of dietary sodium lowers blood pressure in hypertensive and normotensive individuals. DATA SOURCES:- An English-language computerized literature search, restricted to human studies with Medical Subject Heading terms, "hypertension," "blood pressure," "vascular resistance," "sodium and dietary," "diet and sodium restricted," "sodium chloride," "clinical trial," "randomized controlled trial," and "prospective studies," was conducted. Bibliographies of review articles and personal files were also searched. TRIAL SELECTION:- Trials that had randomized allocation to control and dietary sodium intervention groups, monitored by timed sodium excretion, with outcome measures of both systolic and diastolic blood pressure were selected by blinded review of the methods section. DATA EXTRACTION:- Two observers extracted data independently, using purpose-designed forms, and discrepancies were resolved by discussion. DATA SYNTHESIS:- The 56 trials that met our inclusion criteria showed significant heterogeneity. Publication bias was also evident. The mean reduction (95% confidence interval) in daily urinary sodium excretion, a proxy measure of dietary sodium intake, was 95 mmol/d (71-119 mmol/d) in 28 trials with 1131 hypertensive subjects and 125 mmol/d (95-156 mmol/d) in 28 trials with 2374 normotensive subjects. After adjustment for measurement error of urinary sodium excretion, the decrease in blood pressure for a 100-mmol/d reduction in daily sodium excretion was 3.7 mm Hg (2.35-5.05 mm Hg) for systolic (P<.001) and 0.9 mm Hg (-0.13 to 1.85 mm Hg) for diastolic (P=.09) in the hypertensive trials, and 1.0 mm Hg (0.51-1.56 mm Hg) for systolic (P<.001) and 0.1 mm Hg (-0.32 to 0.51 mm Hg) for diastolic (P=.64) in the normotensive trials. Decreases in blood pressure were larger in trials of older hypertensive individuals and small and nonsignificant in trials of normotensive individuals whose meals were prepared and who lived outside the institutional setting. CONCLUSION:- Dietary sodium restriction for older hypertensive individuals might be considered, but the evidence in the normotensive population does not support current recommendations for universal dietary sodium restriction.     

Ideal total hip prosthesis in 1993

Although it is a hazardous adventure to define what is an ideal in any field, it would appear that there is a certain consensus about total hip prostheses. The fundamental principle of the total hip replacement was based on the articulation of a spheric segment, a mobile head contained in a hemispheric non-retaining element. To date, the first material is a titanium in a alloy containing 6% aluminum and 4% vanadium. The second material facing the titanium is polyethylene or alumine. Thus the joint couple could be "polyethylene-metal", or "polyethylene-alumine" or even "alumine-alumine". The hemispheric element can be a massive piece of polyethylene or formed by a peripheral metal (an open hemisphere) filled with the joint surface, itself made of polyethylene. This solution offers the possibility of changing the prosthesis in case of wear without interrupting the implant-bone contact. The first type is cemented to the bone with methyl polymethacrylate. With the second, the metallic part need not to be cemented and can be fitted to the bone by simple pressing. Several points are essential in the femoral piece. It should include a removable head so the length of the neck can be adjusted. It must fill the medullary canal as closely as possible and fill the methaphyseal space. It is fixed by a self-fitting system leading to stable secondary long-term fixation-a porous covering, sometimes with hydroxy apatite can also be useful. In certain cases it must be cemented, although the cement must only play the role of adaptation.(ABSTRACT TRUNCATED AT 250 WORDS)     

An approximate model and empirical energy function for solute interactions with a water-phosphatidylcholine interface

An empirical model of a liquid crystalline (L alpha phase) phosphatidylcholine (PC) bilayer interface is presented along with a function which calculates the position-dependent energy of associated solutes. The model approximates the interface as a gradual two-step transition, the first step being from an aqueous phase to a phase of reduced polarity, but which maintains a high enough concentration of water and/or polar head group moieties to satisfy the hydrogen bond-forming potential of the solute. The second transition is from the hydrogen bonding/low polarity region to an effectively anhydrous hydrocarbon phase. The "interfacial energies" of solutes within this variable medium are calculated based upon atomic positions and atomic parameters describing general polarity and hydrogen bond donor/acceptor propensities. This function was tested for its ability to reproduce experimental water-solvent partitioning energies and water-bilayer partitioning data. In both cases, the experimental data was reproduced fairly well. Energy minimizations carried out on beta-hexyl glucopyranoside led to identification of a global minimum for the interface-associated glycolipid which exhibited glycosidic torsion angles in agreement with prior results (Hare, B.J., K.P. Howard, and J.H. Prestegard. 1993. Biophys. J. 64:392-398). Molecular dynamics simulations carried out upon this same molecule within the simulated interface led to results which were consistent with a number of experimentally based conclusions from previous work, but failed to quantitatively reproduce an available NMR quadrupolar/dipolar coupling data set (Sanders, C.R., and J.H. Prestegard. 1991. J. Am. Chem. Soc. 113:1987-1996). The proposed model and functions are readily incorporated into computational energy modeling algorithms and may prove useful in future studies of membrane-associated molecules.     

Differential effects of elevated potassium ion concentration and of theophylline on growth hormone release by rat adenohypophyses in vitro

The effects of 27 mM K+ and of 6.7 mM theophylline on the release of growth hormone (GH) by rat hemipituitaries in vitro were investigated using bioassay (rat tibia test) and radioimmunoassay (RIA). Both agents markedly increased the release of immunoreactive GH. High K+ also promoted the release of bioactive GH but to a much lesser degree than RIA-GH. Theophylline did not consistently affect the release of bioassay-detectable GH. The results suggest that these agents promote massive release of a form of immunoreactive GH (possibly "immature") that has little or no activity in the bioassay. Theophylline is relatively more effective in this regard than is elevated K+.     

Experimental electrocoagulation of dog esophageal and duodenal mucosa

The per review system for the assessment of research proposals is widely respected by working scientists. Nevertheless two problems associated with the operation of this system by the US National Institutes of Health are identified. First the scientist has no control over which committee will review an application and it may be considered by a quite inappropriate group. Second analysis of the committee composition suggests that in some of the groups several members are not active scientists and therefore not the "peers" of the applicant.