Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study.

BACKGROUND: Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. OBJECTIVE: To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. METHODS: Five subjects with newly diagnosed, treatment-naive relapsing-remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. RESULTS: The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. CONCLUSION: TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

Optimizing dynamic T2* MR imaging for measurement of cerebral blood flow using infusions for cerebral blood volume.

We describe an approach to measuring cerebral blood flow (CBF) based on independent measurements of cerebral blood volume (CBV) and mean transit time (MTT) with calculation of CBF by using the central volume theorem: CBF = CBV / MTT. This permits optimization of the individual acquisitions and analyses. In particular, measurement of CBV during contrast infusion, rather than simultaneously with MTT from a single bolus, yields values more consistent with those of other methods.

An isokinetic investigation of contractile mode's effect on the elbow flexors.

Healthy, sedentary, college-age subjects (n = 16) performed concentric or eccentric maximal unilateral isokinetic (1.08 rad s(-1)) elbow flexor contractions (4 sets of 12 repetitions) to fatigue as physiological data were concurrently collected. Net caloric expenditure was determined using indirect calorimetry, whereas the electromyogram examined root mean square (RMS) and mean power frequency (MPF) values for the biceps brachii, brachioradialis, and palmaris longus. Eccentric exercise resulted in significantly greater (p < 0.05) absolute (total work per kilocalorie) and relative (total work per kilocalorie per kilogram) exercise efficiency values. Concentric biceps brachii and brachioradialis RMS values were significantly (p < 0.05) greater than corresponding eccentric values, suggesting greater motor unit recruitment. Concentric MPF values, a measure of motor unit fatigue, showed significantly (p < 0.05) greater before and after decrements following exercise for the biceps brachii and brachioradialis. Greater exercise efficiency with less motor unit recruitment and fatigue results from eccentric exercise.

Relationships between throwing mechanics and shoulder distraction in professional baseball pitchers.

The extreme forces and torques and the high speeds and excessive ranges of motion of baseball pitching place tremendous stress on the soft tissues of the throwing shoulder. Little is known about the relationship between pitching mechanics and shoulder joint stress, especially in professional athletes. The purpose of this study was to quantify joint loads and kinematic parameters of pitching mechanics at the major league level and to study their relationships. Three-dimensional, high-speed video data were collected on 40 professional pitchers during the 1998 Cactus League spring training. A clinically significant distraction force was calculated at the shoulder joint, which reached an average peak value of 947 +/- 162 N (108% +/- 16% body weight). Descriptive statistics and a multiple linear regression analysis were used to relate shoulder distraction to kinematic and kinetic parameters of pitching mechanics. This study was undertaken not only to investigate the peak forces and torques on the shoulder, but also to identify potential areas of intervention that might prevent throwing injuries. Knowledge of joint ranges of motion, angular velocities, and joint-reaction forces can provide a scientific basis for improved preventive and rehabilitative protocols for baseball pitchers.

The effects of extended play on professional baseball pitchers.

The purpose of this study was to investigate kinematic and kinetic changes as a result of extended play in baseball pitching. Seven major league baseball pitchers were videotaped with high-speed (120 Hz) cameras during multiple innings of the same game. For each athlete, two fastballs (one thrown during the initial inning of play and one from the final inning) were chosen for analysis. Twenty-one physical landmarks were manually digitized from the video data. Kinematic and kinetic parameters were subsequently calculated relative to four phases of the pitching motion: windup, cocking, acceleration, and follow-through. Paired t-tests revealed that seven parameters changed significantly between early and late innings. These included decreases in maximum external rotation of the shoulder, knee angle at ball release, ball velocity, maximum distraction force at both the shoulder and elbow, and horizontal adduction torque at both release and its maximum value. Ultimately, a decline in performance was evident by a 2 m/s (5 mph) drop in ball speed. It is unclear whether the kinematic and kinetic changes occurred because of fatigue or if protective mechanisms were adopted.

Adjusting survival analysis for the presence of unadjudicated study events.

In the Coumadin Aspirin Reinfarction Study (CARS), the primary (efficacy) endpoint was time to the first occurrence of reinfarction, ischemic stroke, or cardiovascular death. Study events likely to be a component of the primary endpoint were reviewed by a blinded Events Classification Committee (ECC). To accommodate the inherent delay imposed by the adjudication process, we used the results of prior adjudication to predict classifications for selected unadjudicated study events in order to conduct "up-to-date" interim analyses for the Data and Safety Monitoring Committee (DSMC). Rates at which previously adjudicated study events were confirmed as primary event components were used to adjust the Kaplan-Meier estimates of survival and the log-rank statistics. Multiple events for a given subject were weighted according to the probability that prior events would be confirmed. Once all study events were adjudicated, final analyses confirmed the results of the adjusted interim analysis. For monitoring clinical trials with adjudicated endpoint events, models based on prior adjudication histories can be reliably used to predict event classifications for unadjudicated events and support accurate, contemporary interim analyses.

Management of giant cell arteritis and polymyalgia rheumatica.

Giant cell arteritis and polymyalgia rheumatica are closely related disorders that affect persons more than 50 years of age and cause substantial morbidity. Patients with giant cell arteritis typically have a localized headache, nonspecific systemic symptoms, temporal artery tenderness and a high erythrocyte sedimentation rate (ESR). The diagnosis is confirmed by characteristic pathologic findings on temporal artery biopsy. Patients with polymyalgia rheumatica usually have similar nonspecific systemic symptoms, proximal muscle pain and stiffness, and an elevated ESR. The diagnosis is based on the clinical findings. Both disorders are treated with corticosteroids: high dosages for giant cell arteritis (prednisone in a dosage of 40 to 60 mg per day) and lower dosages for polymyalgia rheumatica (prednisone in a dosage of 10 to 20 mg per day). Symptom relief in response to treatment is rapid and reinforces the diagnosis. After normalization of the ESR, the corticosteroid is tapered, with the patient monitored closely for symptom recurrence. Most patients require corticosteroid therapy for two to three years and experience one or more treatment complications.

Safety, tolerance, and efficacy of adenosine as an additive to blood cardioplegia in humans during coronary artery bypass surgery.

Myocardial stunning after heart surgery is associated with increased morbidity and mortality in patients with severe multivessel disease and reduced myocardial function. The purpose of this study was to evaluate the safety, tolerance, and efficacy of adenosine as a cardioprotective agent when added to blood cardioplegia in patients undergoing coronary artery bypass surgery. Sixty-one patients were randomized to standard cold-blood cardioplegia, or cold-blood cardioplegia containing 1 of 5 adenosine doses (100 microM, 500 microM, 1 mM, 2 mM, and 2 mM with a preischemic infusion of 140 microg/kg/min of adenosine). Invasive and noninvasive measurements of ventricular performance and rhythm were obtained preoperatively, prebypass, and then at 1, 2, 4, 8, 16, and 24 hours postbypass. Use of inotropic agents and vasoactive drugs pastoperatively was recorded; blood samples were collected for measurement of nucleoside levels. High-dose adenosine treatment was associated with a 249-fold increase in the plasma adenosine concentration and a 69-fold increase in the combined levels of adenosine, inosine, and hypoxanthine (p <0.05). Increasing doses of the adenosine additive were also associated with lower requirements of dopamine (p = 0.003) and nitroglycerine (p = 0.001). The 24-hour average doses for dopamine and nitroglycerine in the placebo group were 28-fold and 2.6-fold greater than their respective high-dose adenosine treatment cohorts. Finally, the placebo- and 100 microM-adenosine group was associated with a lower ejection fraction when compared to patients receiving the intermediate dose or high-dose treatment. These findings are consistent with the hypothesis that adenosine is effective in attenuating myocardial stunning in humans.

The development of occupational aspirations and expectations among inner-city boys.

The occupational aspirations and expectations of two populations of boys in grades 2, 4, 6, and 8 were examined in order (1) to describe what is unique about the development of job preferences among urban ghetto children who live in settings where many adult males are not well attached to the labor force and (2) to examine 6 reasons for any age- and population-dependent patterns there might be in job aspirations and job expectations. Findings show that boys tend to be more realistic about occupational aspirations and expectations the older they are; that from second grade on the occupational expectations of inner-city boys mirror existing race and class differences in adult job holdings; that the gap between occupational aspirations and expectations is greater for the ghetto boys and remains roughly constant in size across the grades examined; and that the lower occupational expectations of the inner-city boys are strongly related to their lower educational expectations, with these educational expectations being associated with fewer poor boys having a biological father at home and with more of these boys seeing obstacles to success in the local social setting. But, the lower occupational expectations of the ghetto boys are not due to having fewer positive role models or believing that schooling will not pay off for them in the future as it does for others.

Adenosine reduces postbypass transfusion requirements in humans after heart surgery.

OBJECTIVE: The objective of this study was to determine the effect, if any, of adenosine blood cardioplegia on blood component usage after heart surgery. SUMMARY BACKGROUND DATA: The most common cause of nonsurgical postcardiopulmonary bypass bleeding is platelet dysfunction. For this reason, pharmacologic agents are under investigation in an effort to reduce the need for transfusion in this setting. METHODS: A posthoc analysis of blood product usage was performed in data obtained from a Phase I, single center, open label, randomized study performed in 63 patients. The trial was designed to test the safety and tolerance of adenosine when added to blood cardioplegia in increasing doses to enhance myocardial protection. The database provided information regarding the effect of adenosine cardioplegia on venous plasma adenosine concentrations, the amount of platelets, fresh frozen plasma and packed erythrocytes used, and the association between the adenosine dose and postoperative thoracic drainage. RESULTS: The postoperative thoracic drainage at 6 hours, 24 hours, and at the time of chest tube removal in the high-dose adenosine cardioplegia group was 68%, 76%, and 75% of the placebo and low-dose adenosine cardioplegia group (p < 0.05). The highest dose of adenosine studied increased baseline adenosine venous plasma levels 360-fold, from 0.17 +/- 0.09 mumol/L to 42.30 +/- 11.20 mumol/L (p < 0.05). This marked increase was associated with a 68%, 56%, and 58% reduction in platelet, fresh frozen plasma, and packed erythrocyte usage, respectively (p < 0.05). CONCLUSIONS: In addition to enhancing the heart's tolerance to ischemia, adenosine-supplemented cardioplegic solution also may reduce bleeding after cardiopulmonary bypass.

Health behavior changes through television: the roles of de facto and motivated selection processes.

We assess the role played by two types of self-selection in accounting for the influence of a television series on smoking cessation. De facto selection is based on respondents' regular channel viewing habits that can expose them to the series. Motivated self-selection takes place when viewers deliberately select to watch television programming because it meets their desire to quit smoking. Self-selection also can be viewed as a methodological artifact, spuriously accounting for the association between the airing of the series and smoking cessation among the target audience. Subjects were a probability sample of Chicago smokers who regularly watch the evening news on one of the network channels. The intervention was a televised self-help smoking cessation program broadcast on one of the network channels over 20 days. Using nested covariance structure models for the analysis, we conclude that 1) de facto selection had no influence on exposure to the program; 2) motivated selection had no influence on exposure to the program; 3) the program reduced smoking; and 4) this effect cannot be attributed solely to the methodological artifact of self-selection, although motivation to quit smoking did have the strongest influence on attempts to quit.

Analysis of variation in prostate-specific antigen values.

This retrospective study analyzes variation in prostate-specific antigen (PSA) levels in 129 males who were not diagnosed with prostate cancer or other known malignancies. The extent to which the assay and the biologic variation contributed to the variation in PSA concentration was evaluated from analysis of slopes characterizing PSA concentration as a function of time. The mean coefficient of variation on observations was 58.0 percent. The estimated mean biologic coefficient of variation was 55.3 percent versus a mean assay coefficient of variation of 13.2 percent, indicating that the assay variation contributed negligibly to variation compared with the biologic variation. The concept that a PSA level which rises more than that attributable to assay variation indicates the need for invasive testing for prostate cancer is questionable. A decreasing PSA level was seen as often and of the same magnitude as an increasing level within a relatively narrow window of approximately one year. We are aware of no reason why this variability in PSA values would not be observed in patients with occult prostate cancer.

The second Chicago televised smoking cessation program: a 24-month follow-up.

OBJECTIVES: As smoking decreases in the population, the remaining smoking population will change, and cessation initiatives will have to incorporate strategies designed for these smokers. METHODS: To study patterns of response to a cessation intervention composed of 20 televised segments and the American Lung Association Freedom from Smoking in 20 Days manual, this study compared cessation rates over 24 months in a cohort of smokers who registered for a cessation program with those in a cohort selected from the smoking population at large. RESULTS: At post intervention, multiple point prevalence of cessation among participants, adjusted for baseline smoking, was 14% among registrants and 6% in the population; at 24 months the adjusted rates were 6% and 2%, respectively. Heavy smokers benefited more than light smokers, and there was a consistent dose-response relationship between extent of exposure to the intervention and cessation. CONCLUSION: The effects of the intervention were strongest for those who read the manual and watched the programs daily. Manual use was important, and those who did not read it did not appear to benefit. Compared to the population and given full participation, heavy smokers benefited more than lighter smokers.

Characteristics of participants in a televised smoking cessation intervention.

Participants in various components of a televised self-help smoking cessation program, based on the American Lung Association's Freedom From Smoking in 20 Days, are compared with a sample of the population of smokers to whom the intervention was addressed. Over 325,000 smokers in the target population were exposed to the program at some level. Most watched televised segments. Approximately 75,000 manuals were distributed and about 55,000 were used. Comparisons between participants and the targeted smoking population indicate that the intervention attracted those in the smoking population who are expected to be the majority of smokers by the Year 2000-blacks, females, and those with incomes under $13,000 per year. Participants with these characteristics were most likely to view the televised segments. Heavy smokers, females, and those with the most education were most likely to refer to the manual at least twice a week during the intervention. Older, nonblack participants and those with incomes of $13,000 or more per year were most likely to attend group support sessions outside the home. Overall, the patterns of association indicate that although a televised smoking cessation program can attract individuals similar to those projected to be smokers in 2000, participation in various components of the intervention will vary by demographic characteristics.

Enhancing surgical nurses' patient education: development and evaluation of an intervention.

This research tested whether staff nurses could provide enhanced patient education and whether increases in education improved surgical patient outcomes. A protocol for patient education was developed from earlier research. Then a multifocal intervention was implemented to motivate and teach staff nurses and to increase structural support for patient education. Following the intervention, patients reported receiving more preoperative information and psychosocial support, but not skills training. These increases occurred without measurable opportunity costs in other areas of nurses' work and generalized to nontargeted patient groups. Concomitantly, patients experienced shortened postoperative hospital stays and decreased use of anti-emetics/sedatives and hypnotics, demonstrating the clinical effectiveness of the increased education.

Clinical and financial effects of psychoeducational care provided by staff nurses to adult surgical patients in the post-DRG environment.

A three-hour, two-stage workshop for staff nurses on providing patient education and psychosocial support was evaluated in terms of its effects on patient welfare and recovery. Subjects were 148 persons who had either a cholecystectomy, other abdominal surgery, or transurethral resection of the prostate (TURP). Two hundred and six additional control subjects were obtained from a nearby hospital. Both hospitals were owned by the same corporation and had many of the same surgeons. After the workshop, experimental subjects used fewer sedatives or antiemetics, fewer hypnotics, and were discharged from the hospital on the average half a day sooner.

Clinical and cost-saving effects of psychoeducational interventions with surgical patients: a meta-analysis.

Meta-analysis of 102 studies was conducted to examine how psychoeducational interventions influence recovery, pain, psychological well-being, and satisfaction with care among hospitalized adult surgery patients. Statistically reliable and positive effects were found on each of these four classes of outcome. Further analyses showed that the effects could not be attributed to biases associated with the decision to publish, low internal validity, measurement subjectively, or a Hawthorne effect. Analyses of the subset of outcomes with most direct cost implications showed that positive, cost-relevant effects were obtained across a wide range of patients, treatment providers, hospital settings, and historic periods.

School Health Education Evaluation. Methodological and substantive significance.

As two of the consultants on the team that advised on design and execution of the School Health Education Evaluation (SHEE), the authors offer retrospective comments on the accomplishments and significance of the study. Comments are divided into three parts. First, the authors point out why many evaluators would argue a priori that the design of the study would not be feasible. Second, the authors discuss why the study did work and what makes it exemplary. Finally, the authors point out the several substantive findings of the study that have broad significance in education beyond health education alone.