Association of factor V activity with membranous vesicles released from human platelets: requirement for platelet stimulation

The membrane-associated factor V-like activity (platelet factor 1, PF1) and the phospholipid-like catalytic surface activity (platelet factor 3, PF3) were studied in human platelets from normal and two factor V-deficient donors. Collagen stimulation or mechanical disruption of gel-filtered platelets was necessary for the expression of significant amounts of PF1 and PF3. Stimulation was also necessary for the uptake of factor V or Va by PF1-deficient platelets from the factor V-deficient donors. The activity of PF1 was also generated by association of factor V or Va with membrane-rich fractions obtained by gel filtration of the supernatant from collagen-stimulated or frozen-thawed PF1-deficient platelets. The amount of PF1 obtained by such all-or-none binding experiments was directly proportional to the amount of PF3 already expressed in the platelet preparation. These data have been summarized in terms of a hypothesis which views PF1 and PF3 to be activities associated with membranous vesicles released from platelets only after stimulation.     

Effectiveness of sampling-exposure procedures on facilities utilization by psychiatric hard-core chronic patients

Sampling-exposure procedures patterned on those of Ayllon and Azrin (1968 a, b) were systematically introduced, alternating with regular pass procedures, in an attempt to increase use of off unit facilities and services by residents of milieu and social-learning treatment units. Social-learning unit residents (for whom passes cost tokens) remained unaffected by the experimental conditions for 22-week duration of the study, using services at a frequency consistently and significantly below that of milieu unit residents (for whom passes were “free”). However, milieu unit residents' utilization was dramatically increased by the sampling-exposure procedures, generalized to alternating announce-only procedures, and continued at a significantly higher level at a final extended baseline.     

Indications, contra-indications, expected results and choice of neoadjuvant chemotherapy for operable breast cancer

Neoadjuvant chemotherapy in breast cancer corresponds to the use of a systemic treatment applied before loco-regional treatment (surgery and/or radiotherapy). Initiated in the seventies for treatment of the locally advanced and/or inflammatory breast cancers, induction chemotherapy has been extended in the beginning of eighties for cancers known as operable (size higher than 3 cm and/or in central position) in order to allow a more frequent conservating surgery. This objective is obtained in 75% of the cases approximately without increase in the risk of local relapse and without noxious effect on overall survival, in spite of the delay of the loco-regional treatment. Neo-adjuvant chemotherapy progressively moved with the advent of major drugs in breast cancer which are anthracyclins, vinorelbine and taxans. But to date, no protocol was essential like an uncontested standard. However, it seems that obtaining a complete clinical response is the best guarantor to avoid relapse. That seems to be observed only after 6 cycles, even 8 cycles of chemotherapy, each cycle combining the 2 major drugs for the treatment of breast cancer of which are anthracyclins and taxanes employed according a sequential scheme after a based-anthracyclins treatment, except any cardiac contra-indication. Moreover, the use of targeted therapeuticals like Herceptin, with a chemotherapy, seems to be promising and should be more studied. Finally, when a neoadjuvant chemotherapy is administered, the evaluation of the pre-treatment biopsy helps to establish key patient-management parameters such as tumour type, SBR grade and immunohistochemical parameters. This evaluation provides predictive parameters with regards to drug response (hormonal status, overexpression of Her2). The further studies realised in this way will permit to improve the results yet obtained.     

Treatment of severe hypophosphatemia.

Aspects of phosphate biochemistry pertinent to therapy, the distribution of phosphorus in body compartments, therapeutic phosphorus preparations, prevention of hypophosphatemia, therapeutic guidelines, and side-effects of phosphorus therapy are reviewed. Severe hypophosphatemia (less than 0.32 mmol/litre or less than 1 mg/dl) can occur with normal or depleted body stores. Because a large amount of phosphorus may shift rapidly between the extracellular and intracellular or bone compartments, the size of a possible total body deficit cannot be estimated from the serum phosphorus level. Similar shifts may occur unpredictably during repair of hypophosphatemia. Therefore, correction of hypophosphatemia in any patient must be empiric and the response of serum levels to therapy should be followed closely. We discuss a method likely to correct hypophosphatemia while minimizing side-effects.     

Binding of alpha-bungarotoxin to proteolytic fragments of the alpha subunit of Torpedo acetylcholine receptor analyzed by protein transfer on positively charged membrane filters.

Proteolytic fragments of the alpha subunit of the acetylcholine receptor retain the ability to bind alpha-bungarotoxin following resolution by polyacrylamide gel electrophoresis and immobilization on protein transfers. The alpha subunit of the acetylcholine receptor of Torpedo electric organ was digested with four proteases: Staphylococcus aureus V-8 protease, papain, bromelain, and proteinase K. The proteolytic fragments resolved on 15% polyacrylamide gels were electrophoretically transferred onto positively charged nylon membrane filters. When incubated with 0.3 nM 125I-labeled alpha-bungarotoxin and autoradiographed, the transfers yielded patterns of labeled bands characteristic for each protease. The molecular masses of the fragments binding toxin ranged from 7 to 34 kDa, with major groupings in the 8-, 18-, and 28-kDa ranges. The apparent affinity of the fragments for alpha-bungarotoxin as determined from the IC50 value was 6.7 X 10(-8) M. The labeling of fragments with alpha-bungarotoxin could be inhibited by prior affinity alkylation of receptor-containing membranes with 4-(N-maleimido)-alpha-benzyltrimethylammonium iodide. These findings demonstrate that immobilized proteolytic fragments as small as 1/5 the size of the alpha subunit retain the structural characteristics necessary for binding alpha-bungarotoxin, although the toxin is bound to the fragments with lower affinity than to the native receptor. The effect of affinity ligand alkylation demonstrates that the alpha-bungarotoxin binding site detected on the proteolytic fragments is the same as the affinity-labeled acetylcholine binding site on the intact acetylcholine receptor.     

ECG patterns confounding the ECG diagnosis of acute coronary syndrome: left bundle branch block, right ventricular paced rhythms, and left ventricular hypertrophy

The ECG has limitations in the evaluation of the chest-pain patient, including the presence of confounding ECG patterns; the ECG patterns that confound the diagnosis of acute myocardial infarction(AMI) include left bundle branch block (LBBB), ventricular paced rhythms (VPR), and left ventricular hypertrophy (LVH). These patterns produce new ST-segment/T-wave abnormalities, which are the new normal findings in these patients and may lead the clinician astray in two distinct instances: (1) diagnosing ECG change related to acute coronary syndromes (ACS) when the abnormality results solely from the confounding pattern; and (2) not acknowledging the confounding nature of these ECG patterns in the evaluation of potential ACS, thereby placing excessive diagnostic confidence in the ECG. This article highlights the diagnostic dilemma encountered in these confounding ECG patterns; the discussion focuses on the expected ECG abnormalities in these patients and the findings seen in ACS.