Sternal wound complications after primary isolated myocardial revascularization: the importance of the post-operative variables.

OBJECTIVE: Select pre-, peri-, and post-operative variables, predictive for sternal wound complications (SWC), in a clinical setting. METHODS: We analyzed pre-, peri-, and post-operative data of 3815 patients who underwent a primary isolated bypass grafting. 100 patients (2.6%) had post-operative SWC. Unifactor and multifactor risk analysis, were used for statistical analysis. RESULTS: Unifactor analysis identified age (P=0.05), obesity (P=0.001), lung disease (P=0.001), extracorporeal circulation >100 min (P=0.02), graft choice (P=0.01), post-operative low cardiac output, reoperation, nephrological, pulmonary problems (P<0.001) as risk factors. Multifactor analysis, identified obesity (P=0.005), reoperation (P=0.01), nephrological (P=0.0001), pulmonary problems (P=0.001) and No-IMA-use (P=0.05) as independent predictors. Age <50 years (P=0.04) decreased the risk for SWC. There is, however, an interaction of the graft-use and the pre-operative and post-operative predictors, that can mask the precise effect of the graft-use. CONCLUSION: Reoperation, nephrological and pulmonary problems are strong predictors, obesity and age independent preoperative risk factors for sternal wound complications.

Discriminative ability of conventional echocardiography and tissue Doppler imaging techniques for the detection of subclinical cardiotoxic effects of treatment with anthracyclines.

This study investigated improvement of diagnosing myocardial damage caused by anthracyclines using tissue Doppler imaging (TDI). The optimal set of conventional echocardiographic and/or TDI parameters, needed for the discrimination of survivors from healthy controls, was retrospectively assessed. A total of 60 patients and 99 controls, age range 8.5 to 17.6 years, were studied. The survivors received 50 to 400 mg/m(2) cumulative dose of anthracyclines, with a mean follow-up of 7.3 (+/-2.3) years. The parameters used in the discriminant score (S-score) were selected from a large set of 51 echocardiographic parameters, using logistic regression analysis (stepwise selection). The correct classification probability (C-index) and the generalized distance (d) between the distributions of S-scores were used to measure the overall discriminative performance of each echocardiographic technique separately and in combination. The overall discriminative performance of the conventional echo-Doppler parameters (C = 77.3%, d = 1.04) was lower than that of the TDI (C = 84.2%, d = 1.37); the highest C-index was obtained using both techniques (C = 89.2%, d = 1.66). The set of parameters includes: LV fractional shortening and MV early diastolic flow velocity, two long-axis and five apical 4-CV TDI wall velocities (systolic and diastolic). In the patient group, the S-score was positively associated with cumulative dose of anthracyclines (p = 0.05) and duration of treatment (p = 0.01). The diagnostic index S-score, based on a limited number of variables from both techniques simultaneously, could retrospectively discriminate asymptomatic children with anthracycline-induced cardiomyopathy from healthy controls. The potentials of the S-score for serial and prospective studies are further investigated.

Predictors of neurological morbidity after coronary artery bypass surgery.

OBJECTIVE: The aim of this study was to analyze the postoperative neurological complications after myocardial revascularization. METHODS: We analyzed the pre-, peri- and postoperative data of 3834 patients who underwent a primary isolated bypass grafting between January 1987 and December 1995. Postoperative neurological complications (A) were divided into mild complications (B) and major complications (C). RESULTS: The incidence of A increased, from 1.4% to 3.0%. Unifactor risk analysis identified: age > 75 years, peripheral vascular atherosclerosis, neurological pathology, aorta-pathology and perioperative myocardial infarction as risk factors for A. Perioperative myocardial infarction and neurological pathology for B; age > 75 years, peripheral vascular atherosclerosis, neurological pathology, perioperative myocardial infarction and aorta pathology for C. Multifactor risk regression analysis identified peripheral vascular atherosclerosis, neurological pathology, aorta-pathology, perioperative myocardial infarction and the time cohort 1993-1995 as independent predictors for A; perioperative myocardial infarction and the time cohort 1993-1995 for B; neurological pathology, aorta-pathology and perioperative myocardial infarction for C. CONCLUSIONS: Peripheral vascular atherosclerosis, neurological pathology, aorta-pathology, the occurrence of a perioperative myocardial infarction and the time cohort 1993-1995 are identified as independent risk factors for neurological complications.

Coronary bypass surgery: what is changing? Analysis of 3834 patients undergoing primary isolated myocardial revascularization.

OBJECTIVE: The patient population undergoing myocardial revascularization has changed during the last few years. Knowledge of these changes, and of the subsequent influence on morbidity and/or mortality is important, not only for up-dating quality control, but also to support decision-making in financial and economical aspects, and in further research concerning coronary artery surgery. METHODS: Pre-, per- and postoperative data of 3834 primary isolated coronary bypass operations, January 1987 December 1995 were analyzed. The total group was divided into three time cohorts. Group A: 1987 1989 (n = 1292); group B: 1990-1992 (n = 1130); and group C: 1993-1995 (n = 1412). RESULTS: Mean age increased from 60.4 +/- 9.0 (S.D.) years in group A to 62.9 +/- 9.9 (S.D.) years in group C (P < 0.0005). Patients with insulin-dependent diabetic (P = 0.005), uro-nefrological (P = 0.002), pulmonary (P < 0.0005)and neurological (P = 0.003) pathology increased significantly, and there was a significant increase in the use of arterial grafts (P < 0.05). Postoperative, hospital mortality remained stable (+/- 2.5%). However, there was a significant increasing percentage of patients with pulmonary (P = 0.04), neurological (P = 0.02) and uro-nefrological (P < 0.0005) problems. CONCLUSION: During the last few years there has been a trend in myocardial revascularization of older patients, with more coexisting disease. Despite the fact that hospital mortality seems stable, there is an increase in major postoperative morbidity.

Insulin stimulates epinephrine release under euglycemic conditions in humans.

In healthy subjects, acute physiological hyperinsulinemia induces activation of the sympathetic nervous system, but in the absence of hypoglycemia, plasma epinephrine levels have not been found to increase during insulin administration. However, the venous level of epinephrine reflects the net result of release, clearance, and uptake and therefore is not a good measure of adrenomedullary epinephrine secretion. The influence of 90 minutes of euglycemic physiological hyperinsulinemia (60 mU x m(-2) x min(-1); plasma insulin concentration, approximately 700 pmol x L[-1]) on epinephrine kinetics using the 3H-epinephrine tracer method was studied in 12 healthy normotensive, non-obese subjects. After bolus injection, [3H]-epinephrine was continuously infused with arterial and venous blood sampling at regular intervals, enabling calculation of total body (systemic) and forearm epinephrine release and clearance. Studies were performed in the basal state and during sympathetic stimulation by lower-body negative pressure (LBNP) of -15 mm Hg for 15 minutes. Control experiments ("sham" clamps, but with LBNP) were performed in four of the 12 individuals. Euglycemic hyperinsulinemia (all arterial glucose samples > or = 4.2 mmol x L[-1]) induced an increase of the arterial epinephrine concentration (P = .03), and tended to increase total body epinephrine release (P = .08). Total body epinephrine clearance did not change during hyperinsulinemia. The insulin-induced increase in forearm blood flow ([FBF] by plethysmography, from 3.0 +/- 0.4 to 3.8 +/- 0.6 mL x dL(-1) x min(-1), P = .01) was strongly correlated with the increase in arterial epinephrine (r = .78, P < .01). Plasma epinephrine concentrations did not change during control experiments (sham clamp). Sympathetic stimulation alone as induced by LBNP did not stimulate epinephrine release. However, the combination of insulin and LBNP significantly increased epinephrine release (from 0.37 +/- 0.06 to 0.56 +/- 0.12 nmol x m(-2) x min(-1), P = .03). We conclude that acute physiological hyperinsulinemia under euglycemic conditions induces epinephrine release. This effect is enhanced when hyperinsulinemia is combined with sympathetic stimulation by LBNP. Due to increased forearm removal, venous epinephrine concentrations hardly change. Epinephrine release was strongly correlated with the hemodynamic effects of insulin.

Measurement by membrane feeding of reduction in Plasmodium falciparum transmission induced by endemic sera.

The standard laboratory test for reduction in malaria transmission is based on the measurement of oocyst numbers in mosquitoes fed on blood meals containing test and control sera. Interpretation of the results, however, is often hampered by the large variation in numbers of infected mosquitoes and oocysts. The objective of this study was to compare 3 measures for the assessment of transmission reduction (so-called R values) and to define the experimental criteria that allow interpretation of the results. To determine variability in R values of control sera, a replicate experiment was performed with 10 non-endemic sera of Dutch blood donors. Furthermore, 2 measures for calculation of transmission reduction were compared in a triplicate experiment using Plasmodium falciparum, Anopheles gambiae and malaria endemic sera. Calculations using the geometric mean of Williams are currently used to identify blocking and non-blocking sera. However, calculations using log-transformed data could distinguish more gradual levels of transmission reduction activity by endemic sera--i.e. blocking, reducing and non-blocking activity. Grading of transmission reduction activity is important for epidemiological studies on transmission immunity and for validation of future transmission-blocking vaccines.

A comparison of transmission-blocking activity with reactivity in a Plasmodium falciparum 48/45-kD molecule-specific competition enzyme-linked immunosorbent assay.

Monoclonal antibodies (MAbs) 32F1 and 32F3 react with two independent epitopes of a protein doublet with molecular weights of 48 and 45 kilodaltons (kD) expressed on the surface of Plasmodium falciparum (Pfs48/45) macrogametes and zygotes; only 32F3 blocks transmission. These MAbs were used to develop a Pfs48/45-specific competition enzyme-linked immunosorbent assay (ELISA) using 32F1 to capture antigen and labeled 32F3 for quantification and analysis of the contribution of antibodies in human serum to transmission-blocking activity. A comparison analysis was used to determine agreement of competition ELISA titers and transmission-blocking activity as observed in the bioassay in three groups of serum samples: 37 from European travelers with previous exposure to malaria, 56 from gametocyte carriers, and 66 from schoolchildren from a malaria-endemic area in Cameroon. The index of agreement between outcomes of the ELISA and transmission-blocking assay in gametocyte carriers and in travelers was specifically defined as fair-to-moderate; in schoolchildren the agreement was not significant. The combined analysis of all sera showed a significant and fair-to-moderate agreement between the results of the competition ELISA and the transmission-blocking assay, with a relative specificity of 94% (of 105 cases negative in the transmission-blocking assay, 99 were also negative in the competition ELISA) and a relative sensitivity of 44% (of 54 cases positive in the transmission-blocking assay, 24 were also positive in the competition ELISA). This study shows that a positive C48/45-ELISA is indicative for transmission-blocking activity in the mosquito assay, while a negative result does not exclude transmission-blocking activity.

Value of the polymerase chain reaction for the detection of Toxoplasma gondii in cerebrospinal fluid from patients with AIDS.

To investigate whether the polymerase chain reaction (PCR) on the BI gene of Toxoplasma gondii could contribute to the diagnosis of cerebral toxoplasmosis in patients with AIDS, we retrospectively tested CSF samples from 20 patients with AIDS suspected of having cerebral toxoplasmosis for the presence of T. gondii. Suspicion of cerebral toxoplasmosis was based on accepted criteria. Nine patients with AIDS with IgG antibodies to T. gondii but who were not suspected of having cerebral toxoplasmosis and four patients with AIDS seronegative for T. gondii served as negative control patients. T. gondii was demonstrated by PCR in the CSF from 13 of the 20 patients with AIDS suspected of having cerebral toxoplasmosis but was not demonstrated in the CSF samples from the nine control patients seropositive for T. gondii and the four control patients seronegative for T. gondii. The data were statistically evaluated. This study shows the value of PCR for the detection of T. gondii in CSF for the diagnosis of cerebral toxoplasmosis in patients with AIDS.

Short-term predictions of HIV prevalence and AIDS incidence.

Reports of AIDS cases in Amsterdam up to February 1990 were used to make predictions of future cases up to 1993. Two published methods were applied, which make extrapolations from current cases and simultaneously estimate the extent of delay in reporting. The choice of the exact model greatly influenced the predictions, as did predictions for distinct transmission groups. We present results for the homo/bisexual male group, and the total population of Amsterdam. The AIDS case predictions are used to predict the HIV prevalence using the ratio of HIV prevalence to AIDS incidence and through 'back calculation'. We suggest that the ratio is a simple technique that may be used to estimate HIV prevalence. The estimated number of cumulative HIV infected homo/bisexual males in Amsterdam in January 1990 was between 2100 and 4100 in a total of 2200-4600 infected people.

Short and medium term projections of the AIDS/HIV epidemic by a dynamic model with an application to the risk group of homo/bisexual men in Amsterdam.

Several methods exist for short term projection of the numbers of AIDS cases. Some use extrapolation of empirical curves fitted to data up to a given time, whereas others such as the popular method of 'back projection' or actuarial methods also use information about the process. In this paper we describe a dynamic model based on a distributed modelling technique allowing for variability both in infectiousness and in age distribution of the population at risk. Some model parameters are taken from the literature, others are estimated from AIDS incidence data from the homo/bisexual population in Amsterdam. The model described here simulates prevalence and incidence of HIV infection. We present prediction intervals for two years from January 1990 onwards. We discuss three scenarios based on the estimated model, two of which consider early treatment with anti-viral drugs. Given the model and the state of the epidemic in Amsterdam, early treatment intervention must be combined with very drastic measures for reducing infectivity in order to have any serious impact on the course of the epidemic.

HIV infection dynamics and intervention experiments in linked risk groups.

A multigroup transmission model is described to study the spread of the human immunodeficiency virus (HIV) in linked risk groups. The model permits simultaneous investigation of the increase in the number of persons infected with HIV in three main risk groups: promiscuous homo/bisexual men (two levels of promiscuity), intravenous drug users (men and women) and promiscuous heterosexual men and women. Three modes of transmission are considered: anal and vaginal intercourse and needle sharing. The high dimensional parameter space is connected with the HIV incidence through a transmission matrix. This matrix summarizes the annual effective contact rates due to the three transmission modes. The model helps to clarify which data are needed to disentangle the relative contribution of the within- and between-group transmission routes. The model can be used to perform theoretical experiments. Given a specification of a baseline, the potential use of the model is illustrated by a simulation describing the effect of blocking the transmission through needle sharing. Reference is made to the HIV/AIDS epidemic in The Netherlands. The results of the study show that the model can play a part in the classification of HIV prevalence patterns in linked risk groups, in the study of the interaction between the main risk groups and in the theoretical evaluation of intervention measures.

Correcting reported AIDS incidence: a statistical approach.

This study is motivated by the time lag between date of diagnosis of AIDS cases and date of reporting, which results in incomplete data about the epidemic. A maximum likelihood procedure has been developed to adjust the actual numbers of diagnosed AIDS cases for reporting delay. If a parametric function for describing past and future incidence is assumed, its parameters and the adjustment for reporting delay can be estimated simultaneously. Data from the WHO Collaborating Centre on AIDS, Paris, are used. Practical problems related to data collection are dealt with.

The biotin-streptavidin system in a two-site ELISA for the detection of plasmodial sporozoite antigen in mosquitoes.

A two-site ELISA has been designed for the detection of sporozoite antigen in mosquitoes. Biotin-labelled monoclonal antibodies against sporozoites and a streptavidin-biotin-peroxidase complex were used to visualize the antigen. Evaluation of the sensitivity and specificity of the procedure was carried out and background levels of reactivity on the basis of negative mosquitoes were calculated. The test has been deliberately kept as simple as possible for use in the tropics and was designed using Anopheles stephensi infected with in vitro cultivated Plasmodium falciparum gametocytes. A minimum of about 100-350 sporozoites could be detected in mature salivary gland infections; in addition sporozoite antigen was detected in mosquitoes several days before the entry of sporozoites into the salivary glands. No reaction was demonstrable either with bloodstage or ookinete antigens of P. falciparum, or with mosquitoes carrying sporozoites of other plasmodial species. The number of sporozoites in positive mosquitoes and the generating capacity of a single oocyst could be assessed by the use of a calibration curve based on dilution data of a known sporozoite suspension. It was found that a single oocyst can produce about 10,000 sporozoite equivalents.

Predicting the dynamic effects of rubella vaccination programmes.

In the Netherlands, prepubertal girls have been vaccinated against rubella since 1974 (the UK strategy). Recently the Dutch Health Council advocated the introduction of an elimination strategy: vaccination of 1- and 9-year-old children. Dynamic effects of both strategies are studied using deterministic and stochastic models. Estimates of several epidemiological parameters are given. All computations and simulations were performed using as much field data as possible. Under the old strategy a new equilibrium is expected around the years 1995 to 2000; the new strategy is estimated to eliminate rubella (CRS) in large parts of the population 3 to 5 years after its initiation. Possible consequences of the new strategy on a cluster of people who refuse vaccination are investigated.

Measles, mumps and rubella: control by vaccination.

In 1984, the Health Council of the Netherlands advised that a new vaccination strategy against measles, mumps and rubella (MMR) should be initiated. The use of a combined MMR vaccine, to be given at 14 months and 9 years of age was recommended. An analysis of this strategy based on mathematical models, predicted that rubella and mumps and very probably measles will be eliminated in The Netherlands before 1990. The use of a combined MMR vaccine has a number of logistical and financial advantages over immunization with separate vaccines. Another factor to be considered is of course the mutual interference regarding immune response or immunization reactions. Less obviously, and often not recognised as an important factor, is the possibility of an adverse effect on the incidence of the congenital rubella syndrome (CRS), when vaccine coverage is low or the natural force of infection of rubella is high. Vaccine induced herd immunity can act to the disadvantage of the unvaccinated individuals. Following earlier work we show that certain vaccination programmes could actually increase the incidence of serious cases. At first sight, this may seem inconceivable. Mathematical analysis, however, reveals that this is indeed a real possibility. Implementing a vaccination programme that is not sufficiently intensive to eradicate the infection in the population will ultimately lead to a new steady state in which the force of infection is lower than in the period before the start of the programme. As a consequence those who are not (effectively) vaccinated have a higher chance of contracting the infection at an older age. For many viral infections, the chance of serious complications is greater if the infection is acquired at an older age. Congenital rubella and measles encephalitis are striking examples (with respect to mumps the situation is less clear). When boys and girls are vaccinated around one year of age and MMR vaccine coverage is lower than approximately 50%, the total number of cases with the congenital rubella syndrome can increase in the long term. When the force of infection of rubella before implementing the vaccination programme is high - which may be the case in developing countries - the effect is more pronounced and even a relatively high vaccine uptake of 80-90% may not be sufficient to keep CRS incidence below the level prior to control.(ABSTRACT TRUNCATED AT 400 WORDS)

Use of the enzyme-linked immunosorbent assay for the early diagnosis of Mycoplasma pneumoniae infection.

IgM and IgG antibodies to Mycoplasma pneumoniae were measured in 147 sera from four groups of patients by means of an indirect enzyme-linked immunosorbent assay (ELISA) and the results compared with those obtained by other methods. A good correlation was demonstrated between the complement fixation test and ELISA-IgM and to a lesser extent ELISA-IgG; for the metabolic inhibition test the reverse was the case. The indirect haemagglutination test appeared to detect mainly IgM antibodies. Low levels of IgM antibodies were detected by ELISA in 60 sera of children not suffering from pneumonia. However, if only high titres (greater than 800) were regarded as indicative of Mycoplasma pneumoniae infection, a presumptive diagnosis could have been made in 42 of 73 single acute phase sera from patients. Comparable results were obtained with IHA. The diagnostic level of IgM antibodies. was reached during the second week of the disease. It is concluded that examination of a single serum sample by either ELISA-IgM or IHA may assist in early diagnosis of Mycoplasma pneumoniae infection.