Evaluation of hypothesis testing for comparing two populations using NONMEM analysis.

In a simulation study of inference on population pharmacokinetic parameters, two methods of performing tests of hypotheses comparing two populations using NONMEM were evaluated. These two methods are the test based upon 95% confidence intervals and the likelihood ratio test. Data were simulated according to a monoexponential model and, in that context, power curves for each test were generated for (i) the ratio of mean clearance and (ii) the ratio of the population standard deviations of clearance. To generate the power curves, a range of these parameters was employed; other pharmacokinetic parameters were selected to reflect the variability typically present in a Phase II clinical trial. For tests comparing the means, the confidence interval tests had approximately the same power as the likelihood ratio tests and were consistently more faithful to the nominal level of significance. For comparison of the standard deviations, and when the volume of information available was relatively small, however, the likelihood ratio test was more able to detect differences between the two groups. These results were then compared to results on parameter estimation in order to gain insight into the question of power. As an example, the nonnormality of estimates of the ratio of standard deviations plays an important role in explaining the low power for the confidence interval tests. We conclude that, except for the situation of modeling standard deviations with only sparse information, NONMEM produces tests of significance that are effective at detecting clinically significant differences between two populations.     

Orthopaedic procedures and prognosis in hemophilic patients who are seropositive for human immunodeficiency virus

Thirty patients who had hemophilia and were seropositive for the human immunodeficiency virus were evaluated. The preoperative CD4 lymphocyte count was decreased to an average of 336 x 10(9) per liter (range, 27 to 708 x 10(9) per liter). After twenty-six orthopaedic operations in patients who had no previous bacterial infection, a nosocomial infection (cellulitis in the forearm, at the site of an intravenous catheter) developed in only one patient, but five patients had an abnormal postoperative fever that was not accompanied by the expected increase in the white blood-cell count. The preoperative CD4 lymphocyte count was significantly reduced in the patients who had an abnormal elevation in body temperature (p less than 0.004). The functional result or outcome after operation was similar to that in hemophilic patients treated before 1982. Subsequent progression of infection with the human immunodeficiency virus, as determined by the CD4 lymphocyte count and the Walter Reed classification system, occurred in most patients. Acquired immunodeficiency syndrome was diagnosed in six patients. A more rapid progression to acquired immunodeficiency syndrome was seen in the patients who had a lower CD4 lymphocyte count preoperatively. Preoperative evaluation of the CD4 lymphocyte count and the response to intradermal skin-test antigens in patients who are at risk for infection postoperatively provides additional information concerning immunological competence. With these data, the possible risk of infection in patients who are seropositive for the human immunodeficiency virus can be estimated more accurately.     

Evaluation by dental students of a communication skills course using professional role-players in a UK school of dentistry

This paper reports student (n = 180) feedback on the role-play teaching methodology used in behavioural sciences teaching at The School of Dentistry in Birmingham (UK). The feedback received on this well-established (since 1995) educational programme was collected via questionnaire (100% response rate), requiring Likert scale and free text responses. Generally students reported that they had enjoyed and valued the session. Over two-thirds (69.7%) of students rated the role-players as 'very real' and over three-quarters (78.9%) rated their feedback as 'very fair'. The data collected from this study will inform future curriculum development. Student feedback was very positive and demonstrated that the cohort (86% of all students studying in years 1, 2 and 3) found the use of professional role-players involved in behavioural sciences teaching to be both acceptable and valuable.     

Flow cytometric analysis of testicular tissue: Detection of injury and recovery

Summary DNA flow cytometry was used to examine the effects of five chemotherapeutic agents, vinblastine, cisplatinum, 5-fluorouracil, cyclophosphamide and Adriamycin, on mouse testes. Alterations in the haploid (1C), diploid (2C) and tetraploid (4C) cell compartments were assessed at 11, 29 and 56 days after giving mice a single intraperitoneal injection of each agent. Analysis of the histograms proved to be a rapid and reproducible method of monitoring injury in this animal model. Because this procedure can detect subtle testicular injuries, it is predicted that DNA histograms obtained from fine needle aspirates will gain increasing acceptance in the management of the oligo- and azoospermic patient.     

Effects of using object self-stimulation as a reinforcer on the prevocational work rates of an autistic child

The purpose of this study was to examine the effects of object self-stimulation on the task-interrupting self-stimulatory behavior and prevocational work responses of a 13-year-old autistic boy. Using a multiple-baseline design across three diferent prevocational tasks, a systematic manipulation of object self-stimulation was associated with increases in correct rates and decreases in task-interrupting self-stimulatory behaviors. An analysis of these data indicates that self-stimulatory behavior may be shaped to facilitate performance proficiencies. Social validation information suggests that favorable generalized responding had occurred. On the basis of findings from this study, future research needs are discussed.     

Behavior, genetics and biochemistry of an allele of the mutant mouse spastic, spaAlb

A new autosomal recessive mutation, characterized by an early defect in righting reflex and stiffened gait, progression to severe spasticity, tremor and rigidity, and death before weaning, appeared spontaneously on the C57BL/6 background. It was shown to be an allele of the mutant spastic spa, and shall be known as spaAlb. Mutant levels of [3H]strychnine binding are less than 10% of control levels in the brainstem and spinal cord. Autoradiographic examination of the distribution of [3H]strychnine binding sites in the mutant confirm a greatly reduced level of binding compared to control in all areas of the spinal cord, brainstem, and midbrain.