Measles in developing countries. Part II. The predicted impact of mass vaccination

A mathematical model is developed to mimic the transmission dynamics of the measles virus in communities in the developing world with high population growth rates and high case fatality rates. The model is used to compare the impacts of different mass vaccination programmes upon morbidity and mortality arising from infection by measles virus. Analyses identify three conclusions of practical significance to the design of optimal vaccination programmes. First, there is no single optimum age at which to vaccinate children for all urban and rural communities in developing countries. For a given community the best age at which to vaccinate depends critically on the age distribution of cases of infection prior to the introduction of control measures. Second, numerical studies predict that the introduction of mass vaccination will induce a temporary phase of very low incidence of infection before the system settles to a new pattern of recurrent epidemics. Mass vaccination acts to lengthen the inter-epidemic period in the post-vaccination period when compared with that prevailing prior to control. Third, numerical simulations suggest that two-phase and two-stage vaccination programmes are of less benefit than one-stage programmes (achieving comparable coverage) aimed at young children. The paper ends with a discussion of the needs for: improved programmes of data collection; monitoring of the impact of current vaccination programmes; and the development of models that take account of viral transmission dynamics, host demography and economic factors.     

FACTORS RELATED TO PERINEAL TRAUMA IN CHILDBIRTH

We conducted an observational cohort study in three nurse-midwifery services to identify patient characteristics and clinical care measures related to perineal trauma at birth. Data were collected on all women who began care with a nurse-midwife in labor, using an adaptation of the Nurse-Midwifery Clinical Data Set (n = 3,049). Study variables included demographics, perineal management techniques and position for birth, and other intrapartum care and events. Univariate and multivariate analyses showed that episiotomy was strongly related to fetal bradycardia, prolonged second stage, ethnic status, and maternal education level. Warm compresses and flexion/counterpressure to slow delivery were protective. Spontaneous lacerations were influenced by these factors as well. The lateral position for birth was protective, and use of oils or lubricants and the lithotomy position increased lacerations. Multisite studies in nurse-midwifery practices may provide an ideal means of determining effective care measures in healthy populations.     

Elevation of plasma thioredoxin levels in HIV-infected individuals

Thioredoxin (Trx), a ubiquitous protein intimately involvedin redox and protein disulfide reductions, has been shown tobe released from cells and to have cytokine-like activities.In addition, Trx has been implicated in the redox regulationof immunological responses and shown to be deficient in tissuesfrom AIDS patients. In studies presented here, plasma Trx levelswere measured by ELISA in plasma samples from HIV-infected individuals(n = 136) and HIV-negative controls (n = 47). To account forthe release of Trx into plasma due to hemolysis, the Trx measurementswere corrected according to the level of hemoglobin in the plasmasample. Data presented show that, in contrast to tissue Trxlevels, corrected plasma Trx levels are significantly higherin HIV-infected individuals than in controls (P < 0.0001).Furthermore, {small tilde}25% of the HIV-infected individualsstudied have plasma Trx levels greater than the highest levelfound in controls (37 ng/ml). Detailed multiparameter FACS analysisof peripheral blood mononuclear cells (PBMC) from the infectedindividuals demonstrates that those with higher plasma Trx levels(37 ng/ml or greater) tend to have lower overall CD4 counts.In addition, increases in plasma Trx levels correlate with decreasesin monochlorobimane staining (indicative of lower intracellularglutathione levels in PBMC) and with changes in surface antigenexpression (CD62L, CD38 and CD20) that occur in the later stagesof HIV infection. These correlations suggest that elevationof plasma Trx levels may be an important component of advancedHIV disease, perhaps related to the oxidative stress that oftenoccurs at this stage.     

Synthesis and pharmacological evaluation of a series of dibenzo[a,d]cycloalkenimines as N-methyl-D-aspartate antagonists.

A series of 73 dibenzo[a,d]cycloalkenimines were synthesized and evaluated for their ability to displace (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]-(+)-10) from its specific binding site on rat cortical membranes. A number of the more active compounds (Ki ranging from 0.006 to 0.21 microM) were evaluated for N-methyl-D-aspartate (NMDA) antagonist activity in the rat cortical slice (Kb ranging from 0.08 to 0.9 microM) and anticonvulsant activity in the mouse against NMDA induced convulsions. The ED50 values ranged from 0.22 to 7.76 mg/kg and correlated reasonably well with the Kb determination. In the dibenzo[a,d]cyclohepten-5,10-imine series, the (+)-5S,10R enantiomer displayed consistently higher levels of biological activity. While substitution at the 3-position of (+)-10 with electronegative atoms generally increased in vitro activity, a loss of potency relative to (+)-10 (MK-801) was observed in vivo for all of the compounds tested.     

The use of mathematical models in the epidemiological study of infectious diseases and in the design of mass immunization programmes

The relationship between the number of people vaccinated for an infectious disease and the resulting decrease in incidence of the disease is not straightforward and linear because many independent variables determine the course of infection. However, these variables are quantifiable and can therefore by used to model the course of an infectious disease and impact of mass vaccination. Before one can construct a model, one must know for any specific infectious disease the number of individuals in the community protected by maternally derived antibodies, the number susceptible to infectious the number infected but not yet infectious (i.e., with latent infection), the number of infectious individuals, and the number of recovered (i.e., immune) individuals. Compartmental models are sets of differential equations which describe the rates of flow of individuals between these categories. Several major epidemiologic concepts comprise the ingredients of the model: the net rate of infection (i.e., incidence), the per capita rate of infection, the Force of Infection, and the basic reproductive rate of infection. When a community attains a high level of vaccination coverage, it is no longer necessary to vaccinate everyone because the herd immunity of the population protects the unvaccinated because it lowers the likelihood of their coming into contact with an infectious individual. Many infections that confer lasting immunity tend to have interepidemic periods when the number of susceptibles is too low to sustain an epidemic. Mass vacination programs reduce the net rate of transmission of the infective organism; they also increase the length of the interepidemic period. Many diseases primawrily associated with children have much more serious consequences in older people and the question arises as to at what point childhood immunization will successfully prevent the more dangerous incidence of the disease in older cohorts. Mathematical models of disease transmission enable one to predict the course of epidemics, design mass vaccination programs, and be guided as to what are the relevant data that should be collected.     

Normative study of grip and wrist flexion strength employing a BTE Work Simulator

The BTE Work Simulator is used in strengthening and endurance programs providing objective information concerning a patient's progress from such programs. This study establishes normative data for grip and wrist flexion strength employing a BTE Work Simulator. For each part of this study, the right hand of 200 normal men between the ages of 30 and 40 years were tested. This study has established benchmark or reference values for the BTE Work Simulator. Normative values provide both objective data, for comparison of the patient to the general population, and long-term goals for which to strive during the rehabilitation process.     

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

REPERFUSION FOLLOWING MYOCARDIAL ISCHAEMIA ENHANCES INOSITOL PHOSPHATE RELEASE IN THE ISOLATED PERFUSED RAT HEART

1. Global myocariial ischaemia (MI) for periods greater tan 5 min caused an inhibition of phosphatidylinositol specific phospholipase C (PtdIns-PLC) activity. 2. Two min reperfusion following a 20 min MI period, a time point associated with reperfusion-induced arrhythmias, resulted in an activation of PtdIns-PLC activity, dependent on endogenous noradrenaline and mediated via al-adrenoceptors. 3. This 2 min reperfusion response, in contrast to healthy myocardium, resulted in: (i) enhanced PtdIns-PLC activity; (ii) increased sensitivity to endogenous noradrenaline; (iii) rapid increases in inositol(1,4,5)trisphosphate (Ins(1,4,5)P3); and (iv) PLC hydrolysis primarily of PtdIns(4,5)P₂, such that the majority of InsP isomers derive from Ins(1,4,5)P₃. 4. Together, these data suggest a functional role for Ins(1,4,5)P3 under postischaemic reperfusion conditions, and provide a possible link between al-adrenoceptor stimulation of the PtdIns turnover pathway and reperfusion injury.     

Effect of pindolol on endocrine and temperature responses to buspirone in healthy volunteers

Ten healthy subjects received buspirone (30 mg orally) with and without pre-treatment with the 5-HT1A receptor antagonist, pindolol (80 mg over 3 days). Following pindolol treatment the growth hormone and hypothermic responses to buspirone were significantly decreased. There was also a delay in the onset of the prolactin response to buspirone but the total amount of prolactin secretion, calculated as area under the curve, was not significantly reduced. The data suggest that the growth hormone and hypothermic responses to buspirone in humans are mediated by 5-HT1A receptors, but an explanation founded on pharmacokinetic factors cannot presently be excluded. Both this latter possibility and the lack of selectivity of pindolol for 5-HT receptors indicate the need for the further neuroendocrine studies of the mode of action of buspirone, preferably with more selective 5-HT1A receptor antagonists.