Congenital hypopituitarism as a cause of undetectable estriol levels in the maternal triple-marker screen

We are reporting a child with congenital panhypopituitarism, in whom deficient fetal steroidogenesis was suspected prenatally because of undetectable estriol levels measured in the maternal triple-marker screen. No fetal abnormalities were detected by ultrasonography. Amniocentesis demonstrated a normal 46,XX karyotype. Measurement of maternal urinary steroids failed to show elevation in the excretion of the major precursor for estriol, 16 alpha-hydroxydehydroepiandrosterone, indicating that the fetus did not have steroid sulfatase deficiency (placental sulfatase deficiency), the most common genetic cause of extremely low estriol. The steroid analysis excluded other rare single gene defects, including aromatase deficiency and 17 alpha-hydroxylase deficiency. We therefore suspected that the cause of low estriol in this fetus was adrenal insufficiency. Postnatal evaluation was consistent with panhypopituitarism, characterized by deficiency of all anterior pituitary hormones. Because this screen is now offered to more than half the pregnant women in the United States, reports of low estriol levels have become increasingly common. Therefore, it is essential that physicians be familiar with the various etiologies, perform the appropriate antenatal evaluation to determine the specific cause, and closely monitor both mother and child ante- and postnatally.     

Modified Larsen scoring of digitized radiographs in rheumatoid arthritis

OBJECTIVE: To facilitate storage, retrieval, and analysis of radiographic images we assessed the validity of a film digitizer and computer based system. METHODS: A total of 101 sets of radiographs of hands and feet from patients with early rheumatoid arthritis were digitized according to standards defined by the American College of Radiology. Two blinded observers applied the modified Larsen score to the digitized images and the original radiographs. RESULTS: There was good concordance between the scoring of digitized images and radiographic films; intraclass correlation coefficient was 0.89. Regression analysis of a Bland-Altman plot revealed that there was no significant systematic bias. It was noted that scoring the digital images took more than twice as long as scoring the radiographic films. CONCLUSION: Our results indicate that modified Larsen scoring of adequately digitized films on standard computer displays is valid and shows good agreement with conventional techniques. Scoring digitized images appears to require more time, but this may be outweighed by the considerable advantages of computer storage and retrieval of radiographic images.     

Pragmatic controlled clinical trials in primary care: the struggle between external and internal validity

Background  

Controlled clinical trials of health care interventions are either explanatory or pragmatic. Explanatory trials test whether an intervention is efficacious; that is, whether it can have a beneficial effect in an ideal situation. Pragmatic trials measure effectiveness; they measure the degree of beneficial effect in real clinical practice. In pragmatic trials, a balance between external validity (generalizability of the results) and internal validity (reliability or accuracy of the results) needs to be achieved. The explanatory trial seeks to maximize the internal validity by assuring rigorous control of all variables other than the intervention. The pragmatic trial seeks to maximize external validity to ensure that the results can be generalized. However the danger of pragmatic trials is that internal validity may be overly compromised in the effort to ensure generalizability. We are conducting two pragmatic randomized controlled trials on interventions in the management of hypertension in primary care. We describe the design of the trials and the steps taken to deal with the competing demands of external and internal validity.     

In vitro fatigue behavior of human dentin with implications for life prediction

Although human dentin is known to be susceptible to failure under repetitive cyclic fatigue loading, there are few reports in the literature that reliably quantify this phenomenon. This study seeks to address the paucity of fatigue data through a systematic investigation of the effects of prolonged cyclical loading on human dentin in an environment of ambient temperature Hank's balanced salt solution (HBSS) at cyclic frequencies of 2 and 20 Hz. The "stress-life" (S/N) data thus obtained are discussed in the context of possible mechanisms of fatigue damage and failure in this material. In addition, stiffness loss data collected in situ during the S/N tests are used to deduce crack velocities and the thresholds for such cracking. These results are presented in a fracture mechanics context as plots of fatigue-crack propagation rates (da/dN) as a function of the stress-intensity range (Delta K). Such S/N and da/dN-Delta K data are discussed in light of the development of a framework for a fracture-mechanics-based methodology for the prediction of the fatigue life of teeth. It is concluded that the presence of small (on the order of 250 microm) incipient flaws in human teeth will not radically affect their useful life.     

Review of economic evaluations of radiofrequency catheter ablation for cardiac arrhythmias

A systematic review of current studies on the cost effectiveness of catheter ablation for treatment of tachycardia in adults was undertaken. The results are summarized based on a predefined framework of principles for economic evaluation. Of 192 abstracts identified, only three cost effectiveness studies were identified. Each focused on a different and specific patient group with selected target disorders, and used decision analysis modelling to estimate cost effectiveness. Radiofrequency catheter ablation is likely to be economically attractive compared with drug therapy in adult patients with frequently symptomatic paroxysmal supraventricular tachycardia (radiofrequency catheter ablation dominates drug therapy options) or in ventricular tachycardia patients with pre-existing ischemic coronary disease (cost effectiveness ratio of about US $21,000 per quality adjusted life year), but not in the treatment of asymptomatic Wolff-Parkinson-White syndrome patients. However, these studies evaluated different types of tachycardias in differing patient populations and all are based on United States data, so decision-makers must be cautious when applying these results to a general population with tachycardia in the Canadian context.     

Transitions in health status in older patients with heart failure

BACKGROUND: We aimed to determine transitions in health perception and functional status in older Medicare patients with heart failure. METHODS: We used 1991 to 1994 data from the Medicare Current Beneficiary Survey, a database that combines Medicare claims with yearly longitudinal surveys. We identified 872 patients 65 years or older in 1991 with a diagnostic code of heart failure. RESULTS: At baseline, 58% of the patients rated their general health perception as "fair" or "poor." Over 1 year, 18% of the patients died. Transition matrices revealed that health perception, activities of daily living, and instrumental activities of daily living were strong correlates of mortality; that dramatic changes in health status were relatively uncommon over 1 year among survivors; and that decline was common in patients with "excellent" or "very good" health perception. The prior year's health status and comorbidity were powerful predictors of the subsequent year's health status. CONCLUSION: Many older patients with heart failure have worsening health status over time. Measures of prior health status can help predict chances of functional recovery.     

Molecular cloning of a vaccine antigen against infection with the larval stage of Echinococcus multilocularis

Alveolar and cystic hydatidosis are caused by infection with the larval stages of Echinococcus multilocularis and Echinococcus granulosus, respectively. A host-protective antigen has been identified in E. granulosus. Here we identify the presence of a closely related protein in E. multilocularis, characterize and express a cDNA encoding the antigen (designated EM95), determine the structure of the em95 gene, and demonstrate that the EM95 recombinant protein can be used to induce significant levels of protection against challenge infection with E. multilocularis eggs in mice.