Effect Of Treatment Order Research Articles

Clinical signs, interventions, and treatment course of three different treatment protocols in patients with Crouzon syndrome with acanthosis nigricans.

Crouzon syndrome with acanthosis nigricans (CAN) is a rare and clinically complex subtype of Crouzon syndrome. At three craniofacial centers, this multicenter study was undertaken to assess clinical signs in relation to the required interventions and treatment course in patients with CAN. A retrospective cohort study of CAN was performed to obtain information about the clinical treatment course of these patients. Three centers participated: Erasmus Medical Centre, Rotterdam, the Netherlands; John Radcliffe Hospital, Oxford, United Kingdom; and Hôpital Necker-Enfants Malades, Paris, France. Nineteen patients (5 males, 14 females) were included in the study. All children were operated on, with a mean of 2.2 surgeries per patient (range 1-6). Overall, the following procedures were performed: 23 vault expansions, 10 monobloc corrections, 6 midface surgeries, 11 foramen magnum decompressions, 29 CSF-diverting surgeries, 23 shunt-related interventions, and 6 endoscopic third ventriculostomies, 3 of which subsequently required a shunt. This study demonstrates that patients with the mutation c.1172C>A (p.Ala391Glu) in the FGFR3 gene have a severe disease trajectory, requiring multiple surgical procedures. The timing and order of interventions have changed among patients and centers. It was not possible to differentiate the effect of a more severe clinical presentation from the effect of treatment order on outcome.

Acute Caffeine Supplementation Does Not Improve Performance in Trained CrossFit® Athletes.

Caffeine’s ergogenic effects persist during various exercise modalities; however, information establishing its efficacy during CrossFit® protocols is limited. This study aimed to determine the effects of caffeine supplementation on CrossFit® performance. Twenty CrossFit®-trained men (age = 26.7 ± 6.2 years, experience = 3.7 ± 2.9 years) were randomized in a double-blind, crossover design. Participants completed two sessions separated by a seven-day washout period, 60 min after consuming 5 mg/kg body mass of caffeine or a placebo. In each session, participants completed as many rounds as possible in 20 min of five pull-ups, 10 push-ups, and 15 air squats. CrossFit® performance was the total number of repetitions completed in 20 min. Paired-samples t-tests were used to compare CrossFit® performance between caffeine and placebo conditions and to test for a potential learning effect between the first and second sessions. CrossFit® performance was not significantly different during the caffeine condition compared to the placebo (468.6 ± 114.7 vs. 466.7 ± 94.3 repetitions, p = 0.861). A significant learning effect was identified between the first and second sessions (452.4 ± 101 vs. 483.8 ± 106.5 repetitions, p = 0.001), with no significant effect of treatment order (p = 0.438). Caffeine’s ergogenic effect were not present during the CrossFit® workout “Cindy”; however, future research should include familiarization sessions and examine other CrossFit® workouts in novice and women participants.

Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer's Disease

ObjectiveTo investigate the efficacy and safety of nabilone for agitation in patients with moderate-to-severe Alzheimer's disease (AD). DesignThis 14-week randomized double-blind crossover trial compared nabilone to placebo (6 weeks each) with a 1-week washout between phases. SettingPatients were recruited from a long-term care facility and geriatric psychiatry clinics. ParticipantsPatients had AD (standardized Mini-Mental State Examination [sMMSE ≤24]) and agitation (Neuropsychiatric Inventory-Nursing Home version [NPI-NH]-agitation/aggression subscore ≥3). InterventionNabilone (target 1–2 mg) versus placebo. MeasurementsThe primary outcome was agitation (Cohen Mansfield Agitation Inventory [CMAI]). Secondary outcomes included NPI-NH total, NPI-NH caregiver distress, cognition (sMMSE and Severe Impairment Battery [SIB] or Alzheimer's Disease Assessment Scale of Cognition), global impression (Clinician's Global Impression of Change [CGIC]), and adverse events. ResultsThirty-nine patients (mean ± SD age = 87 ± 10, sMMSE = 6.5 ± 6.8, CMAI = 67.9 ± 17.6, NPI-NH total = 34.3 ± 15.8, 77% male, nabilone dose = 1.6 ± 0.5 mg) were randomized. There were no crossover or treatment-order effects. Using a linear mixed model, treatment differences (95% CI) in CMAI (b = −4.0 [−6.5 to −1.5], t(30.2) = −3.3, p = 0.003), NPI-NH total (b = −4.6 [−7.5 to −1.6], t(32.9) = −3.1, p = 0.004), NPI-NH caregiver distress (b = −1.7 [−3.4 to −0.07, t(33.7) = −2.1, p = 0.041), and sMMSE (b = 1.1 [0.1–2.0], t(22.6) = 2.4, p = 0.026) all favored nabilone. However, in those who completed the SIB (n = 25) treatment differences favored placebo (b = −4.6 [−7.3 to −1.8], t(20.7) = −4.8, p = 0.003). CGIC improvement during nabilone (47%) and placebo (23%) was not significantly different (McNemar's test, exact p = 0.09). There was more sedation during nabilone (45%) compared to placebo (16%) phases (McNemar's test, exact p = 0.02), but treatment-limiting sedation was not significantly different (McNemar's test, exact p = 0.22). ConclusionsNabilone may be an effective treatment for agitation. However, sedation and cognition should be closely monitored.

The Effects of Acute Caffeine Supplementation on Performance in Trained CrossFit Athletes.

Caffeine’s ergogenic effects persist during various exercise modalities; however, information establishing its efficacy during CrossFit protocols is limited. Our study aimed to determine the effects of caffeine supplementation on CrossFit performance. Thirteen CrossFit-trained men (age = 28.5 ± 6.6 years, experience = 49.2 ± 36.3 months) were randomized in a double-blind, crossover design. Participants completed two sessions separated by a seven-day washout period, 60 min after consuming 5 mg/kg body mass of caffeine or a placebo. In each session, participants completed as many rounds as possible in 20 min of 5 pull-ups, 10 push-ups, and 15 air squats. CrossFit performance was the total number of repetitions completed in 20 min. Paired samples t-tests were used to compare CrossFit performance between caffeine and placebo conditions and to test for a potential learning effect between the first and second sessions. CrossFit performance was significantly higher during the caffeine condition compared to the placebo (461.4 ± 103 vs. 425.0 ± 93.5 repetitions, p < 0.05). No significant learning effect was identified between the first and second sessions (445.6 ± 95.0 vs. 440.8 ± 105.0 repetitions, p = 0.73) nor was there a significant treatment order effect (p = 0.40). Caffeine’s ergogenic effect is present during CrossFit; however, future investigations should establish caffeine’s efficacy during other CrossFit protocols and among female athletes.

Functional Neuroimaging Guided Active Rehabilitation for PCS: A Retrospective Comparative Study of an NVC-Targeting Therapeutic Approach

Background: Recent work has demonstrated several advancements in therapeutic options for patients with postconcussion syndrome (PCS). Specifically, active rehabilitation has emerged as a promising direction for the best treatment outcomes. Enhanced Performance in Cognition (EPIC) is one form of active rehabilitation for PCS that uses a multi-disciplinary clinical approach focusing on two primary aims: the objective diagnosis of PCS using a quantitative, biomarker-based form of fMRI, and targeted neurorehabilitation. The targeting and rehabilitation of the neurovascular coupling (NVC) unit is an essential and novel component of this approach. This study seeks to contribute to the current field of active PCS therapy by demonstrating the usefulness of targeting NVC dysfunction. Further, we compare the EPIC protocol to treatment as usual using a retrospective comparative study design. Methods: The principal cohort was designated as all patients who received EPIC treatment from the time original pilot data was published to the time of retrospective data analysis and chart review (June 2016-October 2017) (N=375). Pre- and post-EPIC post-concussion symptom scales (PCSS) and severity index scores (SIS) were measured and compared. Then, based on pre-specified inclusion criteria for chart review, two patient cohorts were retrospectively assigned to treatment order 1 (TO1: N=15) and treatment order 2 (TO2: N=28). SIS was measured at pre-/post-EPIC and pre-/post-treatment as usual (TAU) functional neurocognitive imaging scans. SIS results from the treatment periods were compared and reported. Results: For the principal cohort (N=375), there was a statistically significant reduction in post-EPIC SIS and PCSS. Concerning the treatment cohorts, there was a highly significant (p<0.0001) overall effect of treatment type on SIS but no such effect of treatment order. However, analysis of TO2 alone revealed a significant effect on SIS reduction (p<0.001) if TAU occurs after EPIC therapy. Conclusion: The findings in this study appear to agree with the current body of research that demonstrates the effectiveness of active rehabilitation strategies compared to standard symptom-modulating and rest-based PCS therapies. Further, EPIC-style therapies contribute to the field of active PCS treatment by addressing NVC disruption in addition to the autoregulatory/vasoreactive aspects of PCS pathophysiology.

Simulating power of economic experiments: the powerBBK package

In this article, we highlight how simulation methods can be used to analyze power of economic experiments. We provide the powerBBK package programmed for experimental economists, that can be used to perform simulations in STATA. Power can be simulated using a single command line for various statistical tests (nonparametric and parametric), estimation methods (linear, binary, and censored regression models), treatment variables (binary, continuous, time-invariant or time varying), sample sizes, experimental periods, and other design features (within or between-subjects design). The package can be used to predict minimum sample sizes required to reach a user-specific level of power, to maximize power of a design given the researcher supplied a budget constraint, or to compute power to detect a user-specified treatment order effect in within-subjects designs. The package can also be used to compute the probability of sign errors—the probability of rejecting the null hypothesis in the wrong direction as well as the share of rejections pointing in the wrong direction. The powerBBK package is provided as an .ado file along with a help file, both of which can be downloaded here ( http://www.bbktools.org ).

Effects of intraperitoneal insulin versus subcutaneous insulin administration on sex hormone-binding globulin concentrations in patients with type 1 diabetes mellitus.

AimsElevated sex hormone-binding globulin (SHBG) concentrations have been described in patients with type 1 diabetes mellitus (T1DM), probably due to low portal insulin concentrations. We aimed to investigate whether the route of insulin administration, continuous intraperitoneal insulin infusion (CIPII), or subcutaneous (SC), influences SHBG concentrations among T1DM patients.MethodsPost hoc analysis of SHBG in samples derived from a randomized, open-labeled crossover trial was carried out in 20 T1DM patients: 50% males, mean age 43 (±13) years, diabetes duration 23 (±11) years, and hemoglobin A1c (HbA1c) 8.7 (±1.1) (72 (±12) mmol/mol). As secondary outcomes, testosterone, 17-β-estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were analyzed.ResultsEstimated mean change in SHBG was −10.3nmol/L (95% CI: −17.4, −3.2) during CIPII and 3.7nmol/L (95% CI: −12.0, 4.6) during SC insulin treatment. Taking the effect of treatment order into account, the difference in SHBG between therapies was −6.6nmol/L (95% CI: −17.5, 4.3); −12.7nmol/L (95% CI: −25.1, −0.4) for males and −1.7nmol/L (95% CI: −24.6, 21.1) for females, respectively. Among males, SHBG and testosterone concentrations changed significantly during CIPII; −15.8nmol/L (95% CI: −24.2, −7.5) and −8.3nmol/L (95% CI: −14.4, −2.2), respectively. The difference between CIPII and SC insulin treatment was also significant for change in FSH 1.2U/L (95% CI: 0.1, 2.2) among males.ConclusionsSHBG concentrations decreased significantly during CIPII treatment. Moreover, the difference in change between CIPII and SC insulin therapy was significant for SHBG and FSH among males. These findings support the hypothesis that portal insulin administration influences circulating SHBG and sex steroids.

Effect of i.p. insulin administration on IGF1 and IGFBP1 in type 1 diabetes

In type 1 diabetes mellitus (T1DM), low concentrations of IGF1 and high concentrations of IGF-binding protein 1 (IGFBP1) have been reported. It has been suggested that these abnormalities in the GH–IGF1 axis are due to low insulin concentrations in the portal vein. We hypothesized that the i.p. route of insulin administration increases IGF1 concentrations when compared with the s.c. route of insulin administration. IGF1 and IGFBP1 concentrations in samples derived from an open-label, randomized cross-over trial comparing the effects of s.c. and i.p. insulin delivery on glycaemia were determined. T1DM patients were randomized to receive either 6 months of continuous i.p. insulin infusion (CIPII) through an implantable pump (MIP 2007C, Medtronic) followed by 6 months of s.c. insulin infusion or vice versa with a washout phase in between. Data from 16 patients who had complete measurements during both treatment phases were analysed. The change in IGF1 concentrations during CIPII treatment was 10.4 μg/l (95% CI −0.94, 21.7 μg/l; P=0.06) and during s.c. insulin treatment was −2.2 μg/l (95% CI −13.5, 9.2 μg/l; P=0.69). When taking the effect of treatment order into account, the estimated change in IGF1 concentrations was found to be 12.6 μg/l (95% CI −3.1, 28.5 μg/l; P=0.11) with CIPII treatment compared with that with s.c. insulin treatment. IGFBP1 concentrations decreased to −100.7 μg/l (95% CI −143.0, −58.3 μg/l; P<0.01) with CIPII treatment. During CIPII treatment, parts of the GH–IGF1 axis changed compared with that observed during s.c. insulin treatment. This supports the hypothesis that the i.p. route of insulin administration is of importance in the IGF1 system.

Effect of dopamine D3 receptor antagonism on approach responses to food cues in overweight and obese individuals

The aim of the study was to examine the effect of manipulating the brain dopamine system, using a D₃ receptor antagonist, on approach responses to food cues in overweight and obese individuals. Twenty-six healthy overweight and obese participants were randomly assigned to receive either a single dose of dopamine D₃ receptor antagonist, GSK598809 (175 mg), or placebo in the first assessment session and vice versa in the second session. Using a stimulus-response compatibility task, approach bias was indexed by response latency to move an image of a manikin towards, versus away from, pictures of food, relative to nonfood stimuli. Data from the first session (which were unaffected by repeated testing) indicated that approach bias scores were significantly reduced in overweight and obese participants who received GSK598809, compared with those who received placebo. Data from the second session were confounded by an effect of treatment order and, consequently, were uninformative for the hypotheses. Between-participant comparison of drug versus placebo conditions indicated that GSK598809 attenuated approach bias to food cues, which is consistent with the reduction in their motivational attractiveness. The findings, albeit preliminary, are in agreement with the view that D₃ receptor antagonists may prove useful as therapeutic agents for reducing appetitive responses to food cues in obesity.

Exploring New Compounds for Functional Imaging Using a Crayfish (Procambarus Clarkia) Aggression Paradigm

Covalently bonding multiple fluorine atom tags to the precursors of monoamines could provide compounds for functional imaging. Theoretically, the fluorine atoms can produce detectible signal if concentrated in vesicles inside neurons. Prior to committing more costly resources to the project, evidence was sought for uptake of the molecules into neurons in living organisms. Two 19F tag configurations of seven or nine atoms were investigated. Crayfish aggression provided a paradigm for obtaining preliminary data on the scarce new molecules. After establishing that 5-hydroxytryptophan (5-HTP) elicited serotonin-like effects, the fluorine tagged versions (PF-5-HTP) were investigated; then, the elevated aggression produced by these precursors to serotonin was blocked by coadministering fluoxetine. Treatment order effects and interrater reliability of the behavioral inventory were evaluated. Preliminary evidence that these imaging compounds are taken up into neurons obtained by studying crayfish behavior later found support using more sophisticated neuroscience techniques.

A Randomized Double‐Blind Study Comparing Rizatriptan, Dexamethasone, and the Combination of Both in the Acute Treatment of Menstrually Related Migraine

To assess the efficacy and tolerability of rizatriptan (RI), dexamethasone (DE), and RI combined with DE (RI+DE) in the acute treatment of menstrually related migraine (MRM). This was a randomized, double-blind, 6-attack crossover study comparing RI 10 mg, DE 4 mg, and RI+DE (2 attacks each). The primary endpoint was 24-hour sustained-relief. The secondary endpoint was 24-hour sustained pain-free. We treated the primary and secondary endpoint as dichotomous outcomes and used matched nonparametric statistics to assess proportions. We used logistic regression to determine the effect of treatment order and if response to previous treatment influenced treatment response. A total of 35 patients treated 190 attacks (mean of 5.4 per participant). For the primary endpoint, RI was significantly superior to DE (62.7% vs 33.3%, P = .001). RI+DE was superior to RI (81.5% vs 62.7%, P < .05) and to DE (81.5% vs 33.3%%, P < .001). For the secondary endpoint RI was also superior to DE (32.2% vs 12.1%, P < .05). RI+DE was superior to RI (50.7% vs 32.2%, P < .05) and DE (P < .01, RR). Similar findings were seen for the other endpoints. More attacks treated with DE+RI (33.8%) were associated with side effects, compared to RI (18.6%) and DE (15.2%). Rizatriptan is an effective treatment for MRM. RI+DE is significantly more effective than RI alone, although is associated with higher rate of adverse events.The combination should be considered for subjects with high disability, incomplete relief, or recurrence of pain with triptan monotherapy.The use of DE alone in the treatment ofMRMis not justified based on our data.

Comparison of the Inhibitory and Excitatory Effects of ADHD Medications Methylphenidate and Atomoxetine on Motor Cortex

Stimulant and norepinephrine (NE) reuptake inhibitor medications have different effects at the neuronal level, but both reduce symptoms of attention deficit hyperactivity disorder (ADHD). To understand their common physiologic effects and thereby gain insight into the neurobiology of ADHD treatment, we compared the effects of the stimulant methylphenidate (MPH) and NE uptake inhibitor atomoxetine (ATX) on inhibitory and excitatory processes in human cortex. Nine healthy, right-handed adults were given a single, oral dose of 30 mg MPH and 60 mg ATX at visits separated by 1 week in a randomized, double-blind crossover trial. We used paired and single transcranial magnetic stimulation (TMS) of motor cortex to measure conditioned and unconditioned motor-evoked potential amplitudes at inhibitory (3 ms) and facilitatory (10 ms) interstimulus intervals (ISI) before and after drug administration. Data were analyzed with repeated measures, mixed model regression. We also analyzed our findings and the published literature with meta-analysis software to estimate treatment effects of stimulants and NE reuptake inhibitors on these TMS measures. There were no significant pretreatment differences or effects of treatment order. Both agents produced a significant increase in facilitation and a decrease in inhibition. Effects of ATX and MPH did not differ significantly. Pooled estimates from published studies show similar results for stimulants and NE reuptake inhibitors. In conclusion, in healthy adults, both stimulant and nonstimulant medications for ADHD decrease cortical inhibition and increase cortical facilitation. Cortical inhibition, shown previously to be abnormal in ADHD, may play a key role producing behavioral pathology.

A prospective, double‐blind, randomized cross‐over study evaluating changes in urinary pH for relieving the symptoms of interstitial cystitis

To provide evidence for the clinical efficacy of changes in urinary pH on the pain associated with interstitial cystitis (IC). A prospective, randomized, double-blind cross-over study was conducted with 26 women with IC between 2000 and 2002, consisting of cross-over instillations of urine at physiological pH (5.0), and neutral buffered pH (NaH(2)PO(4) buffered to pH 7.5). The outcome measured was the subjective symptom of pain assessed using a visual analogue scale at baseline, after the initial instillation of solution, at washout, and after the crossover instillation. Data were analysed using repeated-measures analysis of variance. There was no statistically significant difference between the mean (sd) change from baseline pain scores after instilling neutral buffered solution, at 0.50 (2.78), and acidic solution, at 0.33 (3.43) (P = 0.85). Secondary outcomes were analysed, including baseline variability and treatment-order effects; neither were significantly different between the groups. There was no statistically significant difference in subjective pain scores on instilling urine at physiological pH or sodium-phosphate buffered saline in these patients with IC. Further work is required to define the role, if any, of urinary pH in the pathophysiology and treatment of IC.

GROSS‐MOTOR SKILL ACQUISITION BY PRESCHOOL DANCE STUDENTS UNDER SELF‐INSTRUCTION PROCEDURES

The effects of two training procedures--(a) modeling and praise and (b) self-instruction, modeling, and praise--on complex gross-motor chain acquisition for preschool dance class students were evaluated. Six girls participated in the study. A multiple baseline design across six gross-motor chains with a secondary group comparison for treatment order effects was used. Both procedures were effective in teaching the gross-motor chains. Nevertheless, for 4 of the 6 participants, the self-instruction procedure produced a faster acquisition rate in at least two of the three comparable pairs of gross-motor chains. Furthermore, very early in gross-motor chain acquisition, for five of the six gross-motor chains, the self-instruction condition was associated with faster response acquisition.

Effect of Perindopril on Cerebral Vasomotor Reactivity in Patients With Lacunar Infarction

There is growing evidence that pharmacologic interference with the renin-angiotensin system may reduce risk of stroke, although the mechanism is unclear. Impaired reactivity of cerebral vessels has recently been recognized as a risk factor for stroke. We examined the effect of the angiotensin-converting enzyme (ACE) inhibitor perindopril on cerebral vasomotor reactivity to acetazolamide in patients with lacunar cerebral infarction. We studied a cohort of male patients between 3 and 12 months after lacunar infarction confirmed on computed tomography. Each patient received perindopril 4 mg daily or matching placebo for 2 weeks in a randomized, double-blind, placebo-controlled crossover fashion. A 1-week washout period was observed between dosing periods. Cerebral vasomotor reactivity (increase in middle cerebral artery mean flow velocity in response to intravenous injection of 15 mg/kg acetazolamide) was measured before and after each dosing period using standard Doppler ultrasound techniques. Twelve patients (mean age 63.2+/-2.3 years) completed the protocol. There was no treatment order effect. Cerebral vasomotor reactivity was significantly greater after perindopril treatment (percent change from baseline +18.8+/-10.1% after perindopril, -4.6+/-4.1% after placebo; P=0.032). Dosing with perindopril did not affect resting cerebral blood flow velocity (percent change from baseline +3.1+/-9.5% after perindopril, -0.6+/-5.4% after placebo), nor was there a change in resting blood pressure (+1.8 mm Hg+/-3.1 after perindopril, +1.4 mm Hg+/-2.5 after placebo). This study provides evidence of a significant improvement in cerebral vasomotor reactivity induced by perindopril, beyond any effect on blood pressure. The results suggest a possible mechanism for the beneficial effect of ACE inhibition on stroke risk observed in recent clinical trials, and suggest a role for the renin-angiotensin axis in the pathophysiology of subcortical small vessel disease.

Budesonide but not nedocromil sodium reduces exhaled nitric oxide levels in asthmatic children

Exhaled nitric oxide (ENO) has been proposed as a marker of airway inflammation in asthma and could be useful to evaluate the response to anti-inflammatory treatment. We investigated the effect of budesonide and nedocromil sodium on ENO levels and lung function in asthmatic children. Twenty stable steroid-naı̈ve asthmatic children were randomized in a single blind, cross-over study to receive inhaled budesonide (group A) or nedocromil sodium (group B) for 6 weeks. ENO was measured with a chemiluminescence analyser at baseline and at the end of each treatment period. Repeated-measures ANOVA was carried out. In asthmatic baseline ENO levels [mean 32·5 ppb, 95% confidence interval (CI) 26·4 to 38·7] were significantly higher compared to reference values (8·7 ppb, 95% CI 8·1 to 9·2,P <0·001). There were no treatment-order effect, no carry-over effect and in both groups the response pattern was the same: budesonide significantly lowered ENO levels from 41·0 ppb to 22·8 ppb in group A (mean,P <0·001) and from 22·6 ppb to 13·0 ppb in group B, (mean, P<0·05), while nedocromil did not reduce ENO values (from 24·4 ppb to 22·6 ppb in group B and from 22·8 ppb to 38·0 ppb in group A, mean, P=NS and P<0·01 respectively). After budesonide treatment ENO values of asthmatics were still significantly higher than in healthy children. The baseline values of FEV1and FEF25–75were normal in both groups and no significant changes were observed during the study. In conclusion, our study shows that budesonide, but not nedocromil sodium, significantly reduces ENO levels in stable asthmatic children even in absence of changes in the lung function.

Fish oil in lupus nephritis: Clinical findings and methodological implications

Our objective was to determine the effects of fish oil on renal function, symptoms, and serum lipids in patients with lupus nephritis. A double-blind, randomized crossover trial of fish oil versus placebo (olive oil) was done on 26 patients with confirmed systemic lupus; 21 completed the study. Intervention was fish oil or placebo, 15 g/day, for one year followed by a 10 week wash-out period, and then the reverse treatment for one year. At baseline and six month intervals, we measured platelet membrane fatty acids, indices of renal function, a disease activity index, serum lipid levels, blood pressure, serum viscosity and red cell flexibility. We found that platelet membrane phospholipids were uniformly affected by fish oil supplementation (P < 0.001) but with significant carry-over effects despite a 10 week wash-out period. Glomerular filtration rate and serum creatinine were not affected. A non-significant reduction in mean (SE) 24-hour proteinuria occurred, from 1424.1 mg (442.7) on placebo to 896.7 mg (352.2) on fish oil (P = 0.21). Fish oil lowered serum triglycerides from 1.89 (0.25) mmol/liter to 1.02 (0.11) mmol/liter (P = 0.004). VLDL cholesterol decreased markedly whether patients initially received fish oil or placebo (P = 0.004). The size of the reduction was affected by the order of treatment (P = 0.03), but parallel comparisons were significant before the crossover (P = 0.0006). With the possible exception of bleeding time, no other treatment effects were shown with fish oil. However, treatment order effects were seen in urinary IgG excretion (P = 0.03), whole blood viscosity (P < 0.0001), red cell flexibility (P = 0.004), and bleeding time (P = 0.06). In conclusion, one year of dietary supplementation with fish oil in patients with stable lupus nephritis did not improve renal function or reduce disease activity, but did alter some lipid parameters. Hitherto unreported carry-over effects and treatment order effects caused by the olive oil created a risk of type II error, and bear methodologic consideration in the design of future studies.

Influence of fatty acids on ammonia and amino acid flux from active human muscle

This study examined the dynamics of ammonia and amino acid exchange of human muscle during prolonged steady-state one-legged exercise at 80% of knee extensor maximal work capacity. Subjects (n = 10) performed leg extensor exercise for 1 h (control series), rested for 40 min while an infusion of Intralipid and heparin was begun, and then exercised the contralateral leg with the identical protocol [free fatty acid (FFA) series]. In the control series, ammonia efflux rose progressively, and 4.4 +/- 0.6 mmol were released in 1 h compared with 2.4 +/- 0.5 mmol (P less than 0.05) in the FFA series. The exercise was associated with large effluxes of total amino acids from the active muscle over the hour (12.8 +/- 4.3 and 10.3 +/- 3.3 mmol for control and FFA, respectively). Glutamine and alanine accounted for 47 and 64% of the efflux for the control and FFA series, respectively, while comparable values for essential amino acids were 24 and 20%. The latter implies that a net muscle protein catabolism was occurring during the exercise. The FFA treatment was associated not only with a reduced muscle ammonia release but also with a decreased (P less than 0.05) arterial concentration of nine amino acids (alanine, methionine, lysine, hydroxyproline, serine, glycine, proline, asparagine, and ornithine). Interpretation is limited due to the treatment order effect, but these data are compatible with the hypothesis that plasma clearance was affected by FFA.

A Comparison of Two Approaches to Learning to Detect Harmonic Alterations

The purpose of this study was to evaluate instructional activities and practice techniques of musicians attempting to improve their accuracy in detecting errors in music examples heard. In this study, a commonly recommended practice procedure, keyboard sight-reading, was compared with listening to recorded examples of simple piano works characteristic of those used in college-level class piano courses. The authors randomly assigned 59 college music majors to two groups. One group (Group R) studied examples by sight-reading music excerpts at the keyboard; the other group (Group L) studied the same excerpts by listening to recordings. Both groups were tested using taped examples of the excerpts with harmonic alterations. When data were collected for harmonic alterations not detected (misses) and for errors indicated where none were performed (false alarms), Group L was significantly more accurate (p = .0001) in detecting harmonic alterations than was Group R. The difference between the two groups was the same regarding false alarms (p = .0001). A repeated measures design was employed 2 weeks later with similar results. The data also indicated a possible effect of treatment order (listening first or sight-reading first). Implications are drawn for classroom application and for further study.

Comparison of the effects of testosterone and dihydrotestosterone on the behavior of male cynomolgus monkeys (Macaca fascicularis)

To compare the behavioral effects of testosterone propionate (TP) and diyhdrotestosterone propionate (DHTP) at doses producing plasma levels of androgens within the physiological rage, observations were made on 4 castrated male cynomolgus monkeys during successive 4-week treatment periods while they received 25, 50, 100, 200, 400 and 800 μg of either TP or DHTP SC/day in counterbalanced order. Males were tested with each of the same 4 female partners (16 pairs, 1024 1-hr behavior tests). Males were injected at 1600 hr and blood samples were obtained at 0800 hr (256 samples, 456 hormone determinations). Physiological plasma levels of T resulted from the 200 μg and 400 μg TP treatments, and were associated with significantly increased ejaculatory behavior. Physiological plasma levels of DHT resulted from the 50 μg and 100 μg DHTP treatments, but there were no changes in ejaculatory behavior over the entire DHTP does range used. This difference in the behavioral effects of TP and DHTP, not previously reported for a primate, could not be accounted for by the effects of treatment order, season, long-term behavioral testing, female sexual motivation or behavior reflecting the peripheral action of androgens.