Job stress, absenteeism and coronary heart disease European cooperative study (the JACE study): Design of a multicentre prospective study

Background: The motives, objectives and design of a multicentreprospective study on job stress, absenteeism and coronary heartdisease in Europe (the JACE study) is presented in this paper.Some specific gaps in the reviewed literature are explicitlytapped into by the JACE study. Its objectives are i) to comparethe distributions of the Karasek job stress scales for the samebroad categories of occupations in different European countries(in males and females), ii) to study the predictive power ofthe job stress scales and the job strain model for one yearof sickness absence (in males and females) and iii) to studythe predictive power of the job stress scales and the job strainmodel for a three year incidence of coronary heart disease (Inmales only). Methods: In answering these questions, relationsare studied controlling for gender, age, level of education,company size, physical work risks and shift work, as well astraditional risk factors for CHD (i.e serum cholesterol, serumHDL cholesterol, smoking habits and blood pressure). The JACEstudy is a Biomed 1 concerted action. The JACE group consistsof eight participating centres from six countries, i.e. fromBelgium and Sweden (two centres), France, Italy, Spain, Swedenand The Netherlands (each one centre). The coordination of thegroup is in Brussels. The participating centres brought in over15, 000 European workers to test the hypotheses.     

Prognostic relevance of serum thymidine kinase in primary myelodysplastic syndromes: relationship to development of acute myeloid leukaemia

The aim of this study was to evaluate the possible prognostic relevance of thymidine kinase serum levels (s-TK), an indirect marker of proliferative activity, in myelodysplastic syndromes (MDS). S-TK levels were monitored by means of a radioenzyme assay in 90 patients affected by MDS (22 refractory anaemia, RA; 17 RA with ring sideroblasts, RARS; 21 RA with blast excess, RAEB; 15 RAEB in transformation, RAEB-T; 15 chronic myelomono-cytic leukaemia, CMMoL). Mean s-TK levels (U//tl) measured at diagnosis were 11–9 –12–6 for RA, 11–4–13'6 for RARS, 19–9 – 28–4 for RAEB, 39–6 – 34–3 for RAEB-T and 77–7 – 69–7 for CMMoL (normal values <5U//LI1). With the only exception of a weak relationship with lactate dehydrogenase, no correlation was found between initial s-TK values and other clinical or laboratory parameters, such as age, haemoglobin, white blood cell or platelet count, percentage of bone marrow blasts. MDS patients with s-TK >38 V/fA , a cut-off level selected by means of ROC statistical analysis, showed a significantly shorter survival than those with s-TK <38U//xl (8–2 v 37–4 months, respectively; P < 0–0001). In particular, transformation in acute myeloid leukaemia (AML) occurred in 17/21 (81%) of patients with s-TK >38U//d and 9/69 (13%) of those with lower levels at diagnosis (P < 00001), independently of FAB subtype. High s-TK levels were also useful to predict evolution in AML during the course of the disease in patients with normal initial values. Multivariate analysis confirmed the independent prognostic value of s-TK on both overall survival and risk of acute transformation. We conclude that s-TK may be an important prognostic factor in MDS, strongly correlated with development of AML.     

The Ideal Thrombolytic Agent: GISSI-2 and ISIS-3

Streptokinase (SK) and tissue plasminogen activator (alteplase [tPA]) are by far the most intensively studied thrombolytic agents, but only recently a direct head-to-head comparison (GISSI-2 Trial, in which 12,490 patients have been randomized) has become available to the scientific community. This trial, with its international extension (the International tPA/SK Mortality Trial) recruited more than 20,000 patients, showed that the two drugs tested (SK and tPA) were substantially comparable as far as the clinical events were considered. ISIS-3, the largest randomized clinical trial ever performed, compares SK, tPA, and APSAC in a factorial design. Its results will be available before spring, 1991. It is likely that these two studies, if the results will be consistent, will give a definitive answer about comparison among thrombolytic drugs. As a consequence of that achievement, the interest of the scientific community will possibly be directed towards the long-term prevention of the infarct complications, namely ventricular remodeling and infarct expansion or life-threatening arrhythmias.     

An Implantable Intracardiac Accelerometer for Monitoring Myocardial Contractility

As the myocardium contracts isometrically, it generates vibrations that are transmitted throughout the heart. These vibrations can be measured with an implantable microaccelerometer located inside the tip of an otherwise conventional unipolar pacing lead. These vibrations are, in their audible component, responsible for the first heart sound. The aim of this study was to evaluate, in man, the clinical feasibility and reliability of intracavity sampling of Peak Endocardial Acceleration (PEA) of the first heart sound vibrations using an implantable tip mounted accelerometer. We used a unidirectional accelerometer located inside the stimulating tip of a standard unipolar pacing lead: the sensor has a frequency response of DC to 1 kHz and a sensitivity of 5 mV/G (G - 9.81 m/s^?2). The lead was connected to an external signal amplifier with a frequency range of 0.05–1,000 Hz and to a peak-to-peak detector synchronized with the endocardial R wave scanning the isovolumetric contraction phase. Following standard electro-physiological studies, sensor equipped leads were temporarily inserted in the RV of 15 patients (68 ± 15 years), with normal regional and global ventricular function, to record PEA at rest, during AAI pacing, during VVI pacing, and during dobutamine infusion (up to 20 |mg/kg per min). PEA at baseline was 1.1 G ± 0.5 (heart rate = 75 ± 14 beats/rain) and increased to 1.3 G ± 0.9 (P = NS vs baseline) during AAI pacing (heart rate = 140 beats/min) and to 1.4 G ± 0.5 (P = NS vs baseline) during VVI pacing (heart rate = 140 beats/min). Dobutamine infusion increased PEA to 3.7 G ± 1.1 (P < 0.001 vs baseline), with a heart rate of 121 ± 13 beats/min. In a subset of three patients, simultaneous hemodynamic RV monitoring was performed to obtain RV dP/dt_max, whose changes during dobutamine and pacing were linearly related to changes in PEA (r = 0.9; P < 0.001). In conclusion, the PEA recording can be consistently and safely obtained with an implantable device. Pharmacological inotropic stimulation, but not pacing induced chronotropic stimulation, increases PEA amplitude, in keeping with experimental studies, suggesting that PEA is an index ofmyocardial contractility. Acute variations in PEA are closely paralleled by changes in R V dP/dt_max, but are mainly determined by LV events. The clinical applicability of the method using RV endocardial leads and an implantable device offers potential for diagnostic applications in the long-term monitoring of myocardial function in man.     

Essential drugs policy in Bolivia

Since the publication of the WHO list of essential drugs 10years ago, there has been a growing volume of literature onthe topic. This paper on the experience of essential drugs policyin Bolivia is written in the belief that reports on attemptsto implement drugs policies in individual countries are oneof the most instructive sources of information. Coming intopower in 1982, the democratic Bolivian government set up a centrally-controlledagency to be responsible for the procurement and distributionof drugs, with a view to making basic drugs available throughoutthe country. Despite limited technical and institutional resources,the policy proved administratively and organizationally practical.However problems arose at the political level both because theinterests of the industry and pharmacists were threatened andbecause there was disagreement within the government as to whetherdrugs should be seen as commercial goods or health aids. Theagency set up to implement the drug policy was abolished withintwo months of the neo-liberal government resuming power in 1985- emphasizing the symbolic importance of the agency in the overallhealth policy. Only when those concerned with drug policy atan international level concentrate on the political and culturalobstacles to essential drugs policies, and stop giving priorityto the practical issues of procurement and distribution, willtheir policies gain the credibility which is a prerequisitefor success.     

Conformation and dynamics of the chemotactic peptide formyl-L-methionyl-L-leucyl-L-phenylalanine in solution

Several conformational and dynamic features of the chemotactic peptide formyl-L-methionyl-L-leucyl-L-phenylalanine in solution have been delineated by investigations of NMR and IR spectroscopic parameters. Both 1D and 2D NMR experiments have been performed for detection of scalar and dipolar proton-proton connectivities, whereas ¹³C and ¹H relaxation parameters have been interpreted in terms of molecular dynamics. The main conformation appeared to be unfolded with the three hydrophobic side chains extending in divergent directions with respect to the backbone. The existence of relatively weak inter-molecular hydrogen bonds was demonstrated, involving the formamide end group, with increase in the hydrophobicity of the external surface.