Is a placebo-controlled surgical trial an oxymoron?

Within the context of the new medical methodology of evidence-based medicine, the ethical issues of making the randomized, placebo-controlled, clinical trial part of the matrix of surgical procedure evaluation are discussed. Surgical trials with alternative research design less rigorous than the double-blind, placebo-controlled, randomized trial leave the alternative: implementing surgical procedures based on anecdotal evidence and weaker scientific research. The conundrum of these clinical trials, as it relates to the evaluation of surgical procedures, is that it appears to confound some of the fundamental ethical principles of beneficence and nonbeneficence. The placebo effect with surgery is so strong that "sham surgery" within the clinical trial context is essential and an appropriate component of the ethics of clinical research. A discussion of these issues is presented.     

Inhibitory effects of AH 21-132 in guinea-pig isolated ileum and taenia caeci.

1. AH 21-132 is being investigated as a potential chemotherapeutic agent for bronchial asthma. The present experiments were designed to determine whether AH 21-132 shares the activity of theophylline as an antagonist at adenosine A1 receptors and to assess its potency as a relaxant in intestinal smooth muscle. 2. In the transmurally-stimulated guinea-pig ileum, theophylline (1 mM), but not AH 21-132 (1 and 10 microM), antagonized twitch depression induced by adenosine. Higher concentrations (100 microM and 1 mM) of AH 21-132 themselves had a depressant effect. Neither theophylline (1 mM) nor AH 21-132 (1 and 10 microM) antagonized twitch depression induced by noradrenaline. 3. AH 21-132 (100 microM and 1 mM) depressed maximum contractions of ileum induced by both acetylcholine (ACh) and histamine. 4. In ileum treated with hyoscine (1 microM), AH 21-132 (greater than 10 microM) caused a concentration-dependent depression of the log concentration-effect curve for potassium chloride. 5. Simultaneous extracellular electrophysiological and mechanical recording from taenia caeci showed that AH 21-132 (100 microM-1 mM) inhibited spontaneous tension waves and their associated bursts of electrical spike activity. 6. Intracellular electrophysiological recording from taenia caeci showed that the mechano-inhibitory effect of 1 mM AH 21-132 was accompanied by abolition of spontaneous spike activity. Following spike abolition, the membrane potential assumed a value very close to that observed during periods of electrical quiescence prior to drug exposure. 7. AH 21-132 inhibited the activity of cyclic AMP-dependent and cyclic GMP-dependent phosphodiesterases derived from homogenates of ileal smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Relationship between maternal education and mental retardation in 10-year-old children

We conducted a case-control study of mental retardation (MR) in which case children (aged 10 years) were identified from existing records at multiple sources, primarily the public school systems. Control children were drawn from a roster of public school students not receiving special education services. We found that maternal educational level at the time of delivery was strongly and inversely related to a form of MR not accompanied by other serious neurologic conditions. For this isolated form of MR, maternal educational level was by far the most important predictor from among seven sociodemographic variables examined. There was a significant race-education interaction that indicated a steeper gradient in risk among white mothers than among black mothers. Relative to children of white mothers with 12 years of education, all children of black mothers, except those whose mothers had 16 or more years of education, were at increased risk. The results may be useful as a guide for selecting high-risk groups as candidates for early childhood intervention programs.     

Psychiatric disorders in adopted children: a profile from the Ontario Child Health Study.

Studies of clinical populations suggest that adopted children are overrepresented among children using mental health facilities, whereas studies using non clinical populations of adopted children have reached mixed conclusions about whether or not there is an increased psychological risk associated with adoption. Data from the Ontario Child Health Study, a community survey of children aged four to 16 years, which included a subpopulation of adopted children, were used to: 1. profile the characteristics of adoptive families; 2. examine the strength of adoptive status as a marker for psychiatric and educational morbidity; and 3. determine the extent to which adoptive status has an independent relationship with psychiatric and educational morbidities. The findings were: 1. adoptive mothers were significantly older than non adoptive mothers, but otherwise adoptive families did not differ significantly from non adoptive families, 2. adoption in boys, but not in girls, was a significant marker for psychiatric disorder and poor school performance; adoption in adolescent girls was a significant marker for substance use; and 3. multivariate analyses demonstrated no independent effect of adoption on psychiatric disorder or poor school performance; for adolescents, adoptive status did have an independent relationship with substance use for girls. The implications of these findings will be discussed.     

Ontario Child Health Study follow-up: evaluation of sample loss

This article presents an analysis of sample loss in a 4-year follow-up of children aged 4 to 12 who participated in the Ontario Child Health Study in 1983. Of the 1,617 children participating in the original Ontario Child Health Study, 1,172 (72.5%) were located and enlisted at follow-up in 1987. Based on wave-one assessments, nonparticipants at follow-up tended to have higher levels of psychopathology and family risk variables. Respondents were matched with nonparticipants and differentially weighted to compensate for selective loss. In comparing estimates based on actual (observed) and weighted responses in the follow-up sample, it was found that the effects of sample loss depended on the analytical focus. Evaluations of outcome of disorder and risk for disorder were not affected by sample loss. Evaluation of variables that predict persistence of disorder (prognosis) was affected by a bias toward the null.     

MRI assessment of the bony pelvis may help predict resectability of rectal cancer

OBJECTIVE: The outcome after surgical treatment of rectal cancer may be influenced by the technical difficulty of the operation, which is thought to be affected by pelvic size. The aim of this study was to examine the association between bony pelvic dimensions and CRM involvement. PATIENTS AND METHODS: All patients with primary rectal cancer between December 1999 and January 2002 were studied. Staging was performed by pelvic MRI. Nine pelvic dimensions were measured from the MR images on a workstation. Pathology reports were obtained for all patients and the mesorectal specimen was examined. Technical difficulty was assessed by circumferential resection margin (CRM) involvement. RESULTS: Of 126 patients with primary rectal cancer, 88 had staging MRI and rectal excision; there were significant differences between the sexes in all 9 pelvic dimensions (P < 0.05). In females, the interspinous diameter was significantly shorter in patients with CRM involvement compared with patients with a negative CRM. In female patients predicted to have a negative CRM, the anteroposterior diameter of the inlet, the anteroposterior diameter of the midplane and the transverse diameter of the midplane (interspinous distance) were significantly shorter in patients who actually had a positive CRM compared with those in whom the CRM was negative. In male patients, there was no correlation between pelvic dimensions and CRM status. CONCLUSIONS: In certain patients with rectal cancer, CRM positivity may be predicted from pre-operative MRI pelvic measurements. This may influence the choice of adjuvant therapy.