Biochemical and clinical responses to dichloromethylene diphosphonate (cl2mdp) in paget's disease of bone

Dichloromethylene diphosphonate (Cl₂MDP, or clodronate disodium) is one of the most potent of the known diphosphonates as an inhibitor of bone resorption and differs from EHDP in that it does not inhibit skeletal mineralization. It is one of the second generation diphosphonates now undergoing clinical evaluation. In the study described here Cl₂MDP was given by mouth (800-1600 mg/day for 6 months) to 35 patients with symptomatic Paget's disease of bone. Cl₂MDP induced a marked fall in serum alkaline phosphatase and urinary hydroxyproline to normal or near normal values in all patients. This was accompanied by clinical improvement in all but 4 patients. Cl₂MDP appears to be another effective oral drug for the treatment of Paget's disease of bone and compares favorably with the calcitonins and EHDP.     

Coronary angiographic morphology in unstable angina: comparative observations of culprit lesions in saphenous vein grafts versus native coronary arteries

GOAL: To compare angiographic characteristics of culprit lesions in saphenous vein grafts (SVG) with those in native coronary arteries (NCA) in patients presenting with unstable angina (UA). METHODS: Over 4 years, a total of 445 consecutive patients undergoing coronary angiography and percutaneous coronary intervention during hospitalization for UA were identified using a prospectively collected database. Patients with enzyme or electrocardiographic (ECG) evidence for acute myocardial infarction were excluded. Single culprit lesions in SVGs were identified by angiographic and ECG criteria in 214 patients and in NCAs in 231 patients. Culprit lesions were clearly identifiable by clinical and angiographic correlation in all cases. Morphologic analysis of the culprit lesions was performed using the Ambrose classification. RESULTS: The SVG group had male predominance (86.4% vs. 66.7%; p = 0001) and was older (67.3 +/- 9.9 years vs. 64.0 +/- 12.2 years; p = 0.0017) compared to the NCA group. Left ventricular ejection fraction was lower in the SVG group (53.8 +/- 15.5% vs. 57.5 +/- 15.2%; p = 0.063). There was a higher incidence of thrombotic-appearing lesions in SVG culprit lesions than in NCAs (31.3% vs. 6.5%; p = 0.001). There was also a higher incidence of ulcerated plaque in SVGs (36.9% vs. 22.1%; p = 0.001). Total occlusions were more common in NCAs (13.0% vs. 7.9%; p = 0.084). The composite incidence of thrombus, ulcerated plaque and total occlusion was more frequent in SVG lesions (59.4% vs. 39.8%; p = 0.001). CONCLUSIONS: In UA, culprit lesions of SVGs assessed angiographically demonstrate morphology consistent with ulcerated plaque and thrombus more frequently than lesions in NCAs, but total occlusions are more common in NCAs. Angiographically-evident active thrombotic and ulcerated lesions underlie acute ischemic syndromes more frequently in SVGs than in native vessels.     

Improving the recruitment and return of nurses and allied health professionals: a quantitative study.

The United Kingdom National Health Service (NHS) is continuing to experience recruitment and retention problems of nursing and allied health profession staff. Consequently, the need to study and understand the key factors that encourage or dissuade people to work for the NHS remains a major research and policy issue. This study provides well-focused, independent research to explore how the NHS can be made more attractive for potential new recruits and possible returners. The views of potential recruits and returners interested in working for the NHS as either a qualified nurse, physiotherapist or radiographer were explored through a postal questionnaire survey which achieved a response rate of 23%. Analysis of the results indicate that the strongest predictor of intention to work for the NHS in one of the three professions was the attitude held by respondents. These attitudes in turn were most influenced by the extent to which people perceived that NHS work as a qualified nurse, physiotherapist or radiographer offered positive features, i.e. rewarding career, teamwork and a chance to help people and to get to know them. The views of family and friends regarding working for the NHS were also important as was the belief in one's ability to secure an NHS job.     

Lipid composition of seven APTT reagents in relation to heparin sensitivity

The phospholipid content of different activated partial thromboplastin time (APTT) reagents was determined and compared to heparin sensitivity. The seven reagents included were those most widely used amongst participants of the U.K. National External Quality Assessment Scheme (NEQAS) at the time of study. Heparin sensitivity was assessed using the APTT ratios obtained by more than 300 NEQAS participants on five plasmas prepared from patients receiving unfractionated heparin. The concentrations of three neutral lipids and six phospholipids present in the seven APTT reagents were determined by high-performance thin-layer chromatography (HPTLC) and densitometry. Both the concentrations and the relative percentages of individual phospholipid components varied markedly between reagents. The total phospholipid concentration included a 12-fold range from 16 to 205 microgram/ml. Phosphatidylserine (PS) was completely lacking from one reagent prepared from vegetable material and ranged from 3 to 22 microgram/ml in the other six reagents containing extracts from animal tissue. The concentration of phosphatidylcholine ranged from 3 to 109 microgram/ml. There was no demonstrable relationship between the concentration of any individual lipid components and heparin sensitivity. However, the relative percentage phospholipid composition was important since a lower % of PS or phosphatidylinositol (PI) correlated with increasing heparin sensitivity.     

Effects of Chronic Alcoholism on Perception of Hierarchical Visual Stimuli

Visuospatial processing in chronic alcoholism was investigated by asking subjects to make similarity judgements of hierarchically constructed visual stimuli. Comparison figures were similar to a standard figure at the global or local level. Alcoholics were less influenced by the global patterns in their similarity judgements than were controls. On the WAIS-R Block Design subtest, alcoholics were also more likely than controls to distort the outer configuration of the design. Results indicate that alcoholism affects global processing on both experimental visuoperception tasks and on clinical measures of visuospatial ability. Implications for models of alcoholic dysfunction are discussed.     

The antigonadotropic action of prostaglandin F2 alpha is not mediated by elevated cytosolic calcium levels in rat luteal cells

We have investigated the role of intracellular calcium in the mechanism of action of prostaglandin F2 alpha (PGF2 alpha) in cultured rat luteal cells. PGF2 alpha (1 microM) maximally inhibited LH-stimulated cAMP accumulation and also initiated a transient release of intracellular calcium. Low doses of the calcium ionophore ionomycin also increased intracellular calcium to a similar extent as PGF2 alpha (1 microM), but did not inhibit LH-stimulated cAMP accumulation. Chelation of intracellular calcium with dimethyl bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) (10 microM) attenuated the transient calcium rise stimulated by PGF2 alpha, but did not affect the inhibitory characteristics of PGF2 alpha on LH-stimulated cAMP accumulation. Treatment of luteal cells with EGTA (1 mM) and ionomycin (500 nM) resulted in depletion of intracellular calcium to such an extent that a subsequent exposure of the luteal cells to PGF2 alpha (1 microM) did not elicit any change in intracellular calcium. Depletion of intracellular calcium and ablation of the calcium response to PGF2 alpha, however, did not affect either the dose response or the time course of inhibition of LH-stimulated cAMP accumulation. We conclude that although intracellular calcium is mobilized by PGF2 alpha in cultured rat luteal cells, the antigonadotropic action of PGF2 alpha on LH-stimulated cAMP accumulation is not mediated by this mechanism.