Trends and district variations in the hospital care of childhood asthma: results of a regional study 1970-85.

Trends and district variations in the pre-hospital and hospital care of children aged 0-14 years admitted with acute asthma were surveyed in all 13 districts of a health region by examining case notes for 1970, 1978, and 1985. From 1970 to 1985 there was a substantial increase in admissions and some reduction of hospital stay. Over this time adrenergic drugs remained the most frequently used treatment with a large shift towards selective beta2 agonists administered by nebulisation. Use of corticosteroids fell in the under 5s with a decrease in the parenteral route of administration but rose in the 5-14 age group with an increase in the oral route of administration. There was an increase the use of oral xanthines but this was outweighed by falls in the use of suppositories and in parenteral administration. The use of antibiotics became less frequent and that of sedatives and antihistamines fell to almost nil. There were also important changes in other aspects of management, notably an increase in the use of lung function tests (from 3% to 70%) and falls in the use of chest radiographs, blood tests, bacteriology, and physiotherapy. In nearly all aspects of management there were significant and often very extreme variations in practice between districts, which were unlikely to be explained by differences in morbidity. These variations would be a suitable focus for medical audit, with the aim of establishing which treatment regimens have the best outcome and avoiding unnecessary cost and discomfort. Because early hospital drug treatment is closely related to the type of treatment given before admission such audit activities would need to include general practitioners.     

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.     

Cancer mortality among shoe manufacturing workers: an analysis of two cohorts.

OBJECTIVES: To examine the cancer risk of shoe manufacturing workers and evaluate whether the risk was associated with exposure to leather dust and solvents. METHODS: Data from two historical cohort studies of shoe workers were expanded and analysed in parallel. A total of 4215 shoemakers from England contributing 103 726 person-years at risk and 2008 shoemakers from Florence, Italy, contributing 54,395 person-years at risk were included in the analysis. Exposure to leather dusts and solvents from glues was evaluated on the basis of job title information. Standardised mortality ratios (SMR) were calculated as ratios of observed deaths (Obs) over expected derived from national mortalities. RESULTS: Overall mortality was lower than expected in both cohorts (English cohort: Obs 3314, SMR 81, 95% confidence interval (95% CI) 78-84; Florence cohort: Obs 333, SMR 87, 95% CI 78-97). An increased risk of nasal cancer was found (English cohort: Obs 12, SMR 741; Florence cohort: Obs 1, SMR 909). 10 of the 13 cases occurred among English workers employed in the manufacture of welted boots (SMR 926, 95% CI 444-1703), a sector of the industry thought to have had the highest exposure to leather dust. Mortality from leukaemia was not increased in the English cohort (Obs 16, SMR 89), but was increased in the Florence cohort (Obs 8, SMR 214, 95% CI 92-421); and the highest risk was found among shoe workers in Florence who were first exposed between 1950 and 1959 when exposure to benzene was substantial (Obs 3, SMR 536, 95% CI 111-1566). Some evidence for an excess risk of stomach, bladder, and kidney cancer, as well as multiple myeloma and non-Hodgkin's lymphoma was also found in the Florence cohort only among workers employed in jobs with the highest exposure to solvents. CONCLUSIONS: These findings confirm the associations between exposure to leather dust and nasal cancer and between exposure to benzene and leukaemia in the shoe manufacturing industry and suggest that the risk of other cancers may be increased among workers exposed to solvents or glues.     

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.