Parasitic gut infections

Emerging spore-forming protozoa such as cryptosporidia and microsporidia are becoming major public health problems in developing countries as well as in the developed world. They are a new addition to an already long list of intestinal parasites, but their diagnosis is much more difficult than for well-known protozoa and helminths. Fortunately, enzyme immunoassay and polymerase chain reaction techniques are becoming available not only for the detection of Cryptosporidium parvum and the microsporidia, but also for Entamoeba histolytica and Giardia lamblia. These assays are not only increasing the sensitivity of detection but are also allowing, for the first time, species differentiation such as Entamoeba histolytica/dispar or Encephalitozoon intestinalis/Enterocytozoon bieneusi.     

Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish section of the ERSPC

Background:

We derived estimates of overdiagnosis by polygenic risk groups and examined whether polygenic risk-stratified screening for prostate cancer reduces overdiagnosis.

Methods:

We calculated the polygenic risk score based on genotypes of 66 known prostate cancer loci for 4967 men from the Finnish section of the European Randomised Study of Screening for Prostate Cancer. We stratified the 72 072 men in the trial into those with polygenic risk below and above the median. Using a maximum likelihood method based on interval cancers, we estimated the mean sojourn time (MST) and episode sensitivity. For each polygenic risk group, we estimated the proportion of screen-detected cancers that are likely to be overdiagnosed from the difference between the observed and expected number of screen-detected cancers.

Results:

Of the prostate cancers, 74% occurred among men with polygenic risk above population median. The sensitivity was 0.55 (95% confidence interval (CI) 0.45–0.65) and MST 6.3 (95% CI 4.2–8.3) years. The overall overdiagnosis was 42% (95% CI 37–52) of the screen-detected cancers, with 58% (95% CI 54–65) in men with the lower and 37% (95% CI 31–47) in those with higher polygenic risk.

Conclusion:

Targeting screening to men at higher polygenic risk could reduce the proportion of cancers overdiagnosed.     

Absenteeism Screening Questionnaire (ASQ): A New Tool for Predicting Long-term Absenteeism Among Workers with Low Back Pain

Introduction: Over the last decades, psychosocial factors were identified by many studies as significant predictive variables in the development of disability related to common low back disorders, which thus contributed to the development of biopsychosocial prevention interventions. Biopsychosocial interventions were supposed to be more effective than usual interventions in improving different outcomes. Unfortunately, most of these interventions show inconclusive results. The use of screening questionnaires was proposed as a solution to improve their efficacy. The aim of this study was to validate a new screening questionnaire to identify workers at risk of being absent from work for more than 182 cumulative days and who are more susceptible to benefit from prevention interventions. Methods: Injured workers receiving income replacement benefits from the Quebec Compensation Board (n = 535) completed a 67-item questionnaire in the sub-acute stage of pain and provided information about work-related events 6 and 12 months later. Reliability and validity of the 67-item questionnaire were determined respectively by test–retest reliability and internal consistency analysis, as well as by construct validity analyses. The Cox regression model and the maximum likelihood method were used to fix a model allowing calculation of a probability of absence of more than 182 days. Criterion validity and discriminative capacity of this model were calculated. Results: Sub-sections from the 67-item questionnaire were moderately to highly correlated 2 weeks later (r = 0.52–0.80) and showed moderate to good internal consistency (0.70–0.94). Among the 67-item questionnaire, six sub-sections and variables (22 items) were predictive of long-term absence from work: fear-avoidance beliefs related to work, return to work expectations, annual family income before-taxes, last level of education attained, work schedule and work concerns. The area under the ROC curve was 73%. Conclusions: The significant predictive variables of long-term absence from work were dominated by workplace conditions and individual perceptions about work. In association with individual psychosocial variables, these variables could contribute to identify potentially useful prevention interventions and to reduce the significant costs associated with LBP long-term absenteeism.     

Atheromatous lesions of the proximal aorta. Severe complications of homozygous type IIa hypercholesterolemia in children

Coronary lesions with atheromatous deposits occurring in later childhood characterize homozygous type IIa hypercholesterolaemia and condition the somber prognosis of a disease which affects one subject in a million. However, aortic lesions are constantly found, as shown by routine ultrasonographic and angiographic studies in these children. The walls of the proximal aorta are cardboard-like and thick, the origin of the aorta is narrow and the semilunar aortic valves are thickened. The valvular or supravalvular aortic gradient may be considerable; it is often progressive, but is sometimes stabilized or made regressive by medical treatments combined with plasmapheresis or porto-caval shunt. Aortoplasty or aortic valve replacement being difficult to perform in these patients, more aggressive therapeutic procedures, such as liver or heart transplantation, have been suggested. The last generation cholesterol-lowering drugs seem to offer some hope of success.     

Preparation of factor IX deficient human plasma by immunoaffinity chromatography using a monoclonal antibody

A murine hybridoma clone is described that grows continuously in culture and produces a monoclonal antibody we have called Royal Free Monoclonal Antibody to factor IX No. 1 (RFF-IX/1). This has high affinity for a coagulation site on factor IX. RFF-IX/1 immobilised on sepharose can be used to deplete factor IX from normal human plasma. This immunoaffinity depleted plasma is indistinguishable from severe Christmas disease plasma and can be used as the substrate in a one stage coagulation assay for factor IX. The affinity column has high capacity and can be regenerated so that large scale production from normal plasma of factor IX deficient plasma as a diagnostic reagent is now feasible.     

The effect of hemodialysis and C5a des arg on neutrophil subpopulations

Alterations in neutrophil subpopulations during human hemodialysis or following injection of C5a des arg into rabbits were studied. Whereas baseline peripheral blood neutrophils contained approximately 80% of cells that formed rosettes with IgG-sensitized erythrocytes, neutrophils harvested at the granulocyte nadir (20 min after initiating hemodialysis or the injection of C5a des arg) were markedly depleted of this population. This was seen in a change in ratio of rosette-forming neutrophils (RFN) to non-rosette-forming neutrophils (non-RFN) from 4:1 at 0 time to 1:2 at 20 min. Since non-RFN are less active in assays of adherence and chemotaxis, these alterations in circulating neutrophil populations were reflected in abnormal functional capacity of neutrophils harvested at 20 min. To study the mechanism of RFN depletion, we investigated the ability of C5a des arg to aggregate various human neutrophil suspensions. Unfractionated neutrophils and RFN demonstrated prompt in vitro aggregation in response to C5a des arg, whereas this activated complement fragment induced little aggregation in a population enriched for non-RFN. These results may explain the alterations in neutrophil adherence, chemotaxis, phagocytosis, and bactericidal activity, which have been reported to accompany clinical disorders characterized by in vivo complement activation (i.e., hemodialysis or gram-negative sepsis).     

Dromotropic effects of drug combinations. Initial results bearing on a combination of deslanoside and ajmaline]

The electrophysiological effects of the cardiotropic drugs have been studied in man by the agency of endocavitary electrocardiography. The effects of drug combinations, which are often prescribed therapeutically, have been studied less often. The authors report the results of a preliminary study of the combination of deslanoside with ajmaline in 26 patients; its effects were compared with those using each drug separately. This combination seems to have true dromotropic effects; although deslanoside alone, in the doses used, does not modify conduction below the bundle of His, it can still act synergistically with ajmaline at this level. A detailed study of the pharmacological effects as a function of the original status of conduction shows that at the level above the bundle His, the dromotropic action is quantitively less on healthy conducting tissue than on abnormal tissue. The effects of ajmaline on the conduction times below the bundle seem to be similar whether or not there is any conduction defect under basal conditions. The difficulties in obtaining and interpreting such measurements in man are discussed in the hope of arriving at a general protocol for studying drug combinations.     

Increased biting rate and reduced fertility in sporozoite-infected mosquitoes

Because salivary function and blood location are impaired in sporozoite-infected mosquitoes, we determined whether such pathology also could lead to an increased biting rate. For 5 days, we compared relative daily biting rates of Plasmodium gallinaceum sporozoite-infected mosquitoes (Aedes aegypti) and noninfected mosquitoes with an olfactometer. Mosquitoes then were exposed for 5 min to an anesthetized guinea pig. Infected mosquitoes exhibited a significant increase in olfactometer response which was also reflected in a decreased egg output. We conclude that if duration of contact with a host is limited, then infected mosquitoes may make more attempts at probing before being successful, and thus enhance transmission.