PHARMACOKINETICS OF ALFENTANIL DURING AND AFTER A FIXED RATE INFUSION

Twenty-nine patients (age range 14–81 yr) undergoing orthopaedicsurgery received alfentanil 100 µg kg^–1 given astwo i.v. boluses followed by a fixed rate infusion of 1 µgkg^–1 min^–1 for 44–445 min. Additional 1-mgbolus doses of alfentanil were administered as required. Plasmasamples were assayed for alfentanil using radio-immunoassay.Pharmacokinetic parameters were estimated by a model-independentapproach and by curve-fitting. Regression analysis showed nostatistical relationship between T, CI or Vd and the durationof the infusion, total dose or body weight. We found no significantcorrelation between age and T of alfentanil for patients youngerthan 40 yr. For patients older than 40 yr, T increased linearlywith age. There was no significant decrease in Cl with age,although the lower values for CI (100–200 ml min^–1)were generally found in subjects older than 60 yr. The presentstudy demonstrated that a 100-µg kg^–1 loading doseand a 1-µg kg^–1 min^–1 infusion may be appropriatefor analgesia in general surgical procedures.     

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.     

Long-Term Survival in Patients Treated with Cardiac Resynchronization Therapy: A 3-Year Follow-Up Study from the InSync/InSync ICD Italian Registry

Background: Studies reporting the long-term survival of patients treated with cardiac resynchronization therapy (CRT) outside the realm of randomized controlled trials are still lacking. The aim of this study was to quantify the survival of patients treated with CRT in clinical practice and to investigate the long-term effects of CRT on clinical status and echocardiographic parameters.
Methods: The study population consisted of 317 consecutive patients with implanted CRT devices from eight Italian University/Teaching Hospitals. The patients were enrolled in a national observational registry and had a minimum follow-up of 2 years. A visit was performed in surviving patients and mortality data were obtained by hospital file review or direct telephone contact.
Results: During the study period, 83 (26%) patients died. The rate of all-cause mortality was significantly higher in ischemic than nonischemic patients (14% vs 8%, P = 0.002). Multivariate analysis showed that ischemic etiology (HR 1.72, CI 1.06–2.79; P = 0.028) and New York Heart Association (NYHA) class IV (HR 2.87, CI 1.24–6.64; P = 0.014) were the strongest predictors of all-cause mortality. The effects of CRT persisted at long-term follow-up (for at least 2 years) in terms of NYHA class improvement, increase of left ventricular ejection fraction, decrease of QRS duration (all P = 0.0001), and reduction of left ventricular end-diastolic and end-systolic diameters (P = 0.024 and P = 0.011, respectively).
Conclusions: During long-term (3 years) follow-up after CRT, total mortality rate was 10%/year. The outcome of ischemic patients was worse mainly due to a higher rate of death from progressive heart failure. Ischemic etiology along with NYHA class IV was identified as predictors of death. Benefits of CRT in terms of clinical function and echocardiographic parameters persisted at the time of long-term follow-up.     

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.     

Pigmented apocrine hidrocystoma—a report of two cases and review of the literature

Two cases of pigmented apocrine hidrocystoma in two women aged 47 and 60 years are reported. In both patients the lesion was located in the temporal region. Histopathological examination did not show the nature of the pigment present in both lesions. It is suggested that the pigmentation observed clinically is due to the Tyndall phenomenon.