Effects of a very-low-calorie diet and physical-training regimens on body composition and resting metabolic rate in obese females

Sixty-nine obese females received 90 d of a liquid diet providing 2184 kJ/d in clinical trials. Groups were diet only (C), diet plus endurance exercise (EE), diet plus weight training (WT), or diet plus endurance exercise and weight training (EEWT). Changes in body weight, percent fat, fat weight, and fat-free mass were not different between groups. Declines in resting metabolic rate (RMR) were approximately 7% to approximately 12% of baseline values with no differences among groups. A significant increase in work capacity (approximately 16%) was shown for EEWT. Strength index showed declines of approximately 6% for C and EE and gains of approximately 3% and approximately 10% for EEWT and WT, respectively. These clinical trials did not show advantages of any exercise regimen over diet alone for weight loss, body-composition changes, or declines in RMR. Improvements in work capacity were limited and strength improved in groups that participated in strength training.     

Immunohistochemical localization of pepsinogen A and C containing cells in Barrett's oesophagus

Summary No data are available on the localization of Pepsinogen A (PGA=PG I) and Pepsinogen C (PGC=PG II) positive cells in Barrett's epithelium. Endoscopic biopsy specimens were taken from the columnar epithelium from 23 patients (n=93), and in addition from the cardia from eight healthy control subjects (n=38). The tissue was stained by the immunoperoxidase technique with specific anti-pepsinogen antisera, and double immunostained for PGA and PGC. In the Barrett's epithelium PGA was found in 28 out of 93 biopsy specimens (30.1%) and PGC in 55 out of 93 (59.1%). Chief cells always stained both for PGA and PGC, while clear mucous cells were often PGA– and PGC+. PGA+ and PGC+ cells were found each in 100% of the biopsy specimens with fundic type epithelium, in 21.7% and 70.7% of biopsy specimens with junctional type, in 0% and 26.1% of biopsy specimens with specialized epithelium and in 12.5% and 43.5% of biopsy specimens with mixed junctional/specialized features respectively. Dysplastic epithelium stained always negatively with both anti-pepsinogen antisera. In most control cardia biopsy specimens PGA as well as PGC were demonstrable; occasionally clear mucous glands were PGA– and PGC+.It is concluded that pepsinogen-containing cells can be accurately identified in the Barrett's epithelium; their presence seems related to the histological cell type. Identification of pepsinogen positive cells may contribute to a more accurate morphological classification of the Barrett's epithelium.Presented in part at the Annual Meeting of the American Gastroenterological Association, San Francisco, May 1986     

Differential expression of pepsinogen isozymogens in a patient with Barrett esophagus

The pepsinogen A (PGA) isozymogens in the gastric mucosa and Barrett epithelium of a female patient with Barrett esophagus were studied on different occasions during a 3-year period by electrophoretic analysis of in vivo steady-state pepsinogen in biopsies by activity staining in combination with variant specific monoclonal antibodies and of de novo synthesized pepsinogen by autoradiography. In Barrett epithelium only one (Pg3) or two (Pg3 and Pg5) primary PGA gene products were detected, whereas in gastric mucosal biopsies three (Pg3, Pg4 and Pg5) primary gene products were demonstrated on all occasions. These differences strongly suggest differential expression/activation of individual gene numbers in the PGA gene cluster in Barrett esophagus and are in line with the preneoplastic nature of this condition. The mechanism behind this deregulation is currently under investigation by cell biology and molecular genetic techniques.     

A method for two dimensional multi-segmental kinematic and kinetic analysis of normal and pathological human gait

The application of an integrated gait analysis system in clinical research is described. With this system it is possible to analyse the walking pattern of various groups of patients with regard to foot-floor contact, kinematics and kinetics, using a Selspot system. In order to study various groups of patients an extensive body-segment model adapted to the variety in patient groups is dealt with and is related to data from the literature. Special attention has been paid to the analysis or errors in the quantities used in kinematics and kinetics. The various sources of errors leading to inaccuracy of the data describing the walking pattern are discussed.     

Is Patient Satisfaction After Total Knee Arthroplasty Predictable Using Patient Characteristics and Preoperative Patient-Reported Outcomes?

BackgroundDissatisfaction after total knee arthroplasty (TKA) remains a difficult problem. Patient characteristics and preoperative patient-reported outcomes (PROs) are potential predictors of satisfaction one year after TKA. Being able to predict the outcome preoperatively might reduce the number of less satisfied patients.MethodsA retrospective cohort study on prospectively collected data of 1239 primary TKA patients (ASA I-II, BMI <35) was performed. Primary outcome was degree of patient satisfaction one year after TKA (Numeric Rating Scale (NRS) 0-10). Secondary outcomes were degree of patient satisfaction six months and two years after TKA and being dissatisfied (NRS 0-6) or satisfied (NRS 7-10) at all three time points. Multivariate linear and binary logistic regression analyses were executed with patient characteristics and preoperative PROs as potential predictors.ResultsOne year after TKA, median NRS satisfaction score was 9.0 (8.0-10.0) and 1117 (90.2%) patients were satisfied. BMI, degree of medial cartilage damage, previous knee surgery, Knee injury and Osteoarthritis Outcome Score-Physical Function Short Form score, EQ VAS score, and anxiety were identified as predictors of the degree of patient satisfaction (P = .000, R² = 0.027). Models on secondary outcomes reported R² of 1.7%-7.1% (P < .05). All models showed bad agreement between observed and predicted values for lower NRS satisfaction scores and being dissatisfied.ConclusionThe degree of patient satisfaction and the chance of being dissatisfied or satisfied six months, one, and two years after TKA are predictable by patient characteristics and preoperative PROs but not at a reliability level that is clinically useful.     

Impact of a daily 10-minute strength and flexibility program in a manufacturing plant

In summary, employees' flexibility and mood showed modest improvements following the implementation of a plant-wide, 10-minute, daily flexibility and strength program. The initial six-week pilot study, administered prior to the plant-wide program implementation, successfully assessed program feasibility, assessed the efficiency of program implementation, identified administrative and logistical concerns, and generated pilot data needed to secure managerial support. Despite the noted significant increases in grip strength in the pilot study, no increases were observed following the six months of plant-wide implementation. This may be related to the differences in low average pretest grip strength for the pilot study compared to the higher scores for the main study population. The pilot study subjects may have received a sufficient exercise stimulus to increase grip strength over the course of six weeks. In contrast, this may not have been the case for the main study subjects due to their higher initial mean grip strength. An increased number of exercises designed to directly impact grip strength may be needed to improve this parameter.     

Phase I/II trial of irinotecan plus high-dose 5-fluorouracil (TTD regimen) as first-line chemotherapy in advanced colorectal cancer.

BACKGROUND: We conducted a phase I/II study of weekly irinotecan [30 min intravenous (i.v.) infusion] combined with 5-fluorouracil (5-FU 3 g/m(2) weekly 48 h i.v. infusion, TTD regimen) as first-line chemotherapy for patients with advanced colorectal cancer (CRC). PATIENTS AND METHODS: The maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) in the treatment of gastrointestinal solid tumors (in phase I), and the antitumor activity and toxicity of the recommended phase I dose (in phase II) were determined. RESULTS: Diarrhea was the DLT, and irinotecan 80 mg/m(2) plus 5-FU 3 g/m(2) was the recommended phase I dose. In phase II, the confirmed response rate was 44% [95% confidence interval (CI) 29% to 59%] and the median overall survival was 23.8 months. However, grade 3/4 diarrhea affected 59% of patients and led to withdrawal of three patients. A second cohort of patients studied using the same schedule but with a reduced 5-FU starting dose of 2.25 g/m(2) showed improved tolerance (the incidence of grade 4 diarrhea decreased from 28% to 11% and overall grade 3/4 diarrhea to 56%, with no patient withdrawals) but the confirmed response rate was 28% (95% CI 14% to 45%) and median overall survival was 17.2 months. CONCLUSIONS: We found weekly irinotecan 80 mg/m(2) plus TTD regimen (5-FU 2.25 g/m(2) given as 48-h i.v. infusion) to be a feasible and active combined chemotherapy for the first-line treatment of advanced colorectal cancer.     

Unraveling toxicological mechanisms and predicting toxicity classes with gene dysregulation networks

The use of genes for distinguishing classes of toxicity has become well established. In this paper we combine the reconstruction of a gene dysregulation network (GDN) with a classifier to assign unseen compounds to their appropriate class. Gene pairs in the GDN are dysregulated in the sense that they are linked by a common expression pattern in one class and differ in this pattern in another class. The classifier gives a quantitative measure on this difference by its prediction accuracy. As an in‐depth example, gene pairs were selected that were dysregulated between skin cells treated with either sensitizers or irritants. Pairs with known and novel markers were found such as HMOX1 and ZFAND2A, ATF3 and PPP1R15A, OXSR1 and HSPA1B, ZFP36 and MAFF. The resulting GDN proved biologically valid as it was well‐connected and enriched in known interactions, processes and common regulatory motifs for pairs. Classification accuracy was improved when compared with conventional classifiers. As the dysregulated patterns for heat shock responding genes proved to be distinct from those of other stress genes, we were able to formulate the hypothesis that heat shock genes play a specific role in sensitization, apart from other stress genes. In conclusion, our combined approach creates added value for classification‐based toxicogenomics by obtaining novel, well‐distinguishing and biologically interesting measures, suitable for the formulation of hypotheses on functional relationships between genes and their relevance for toxicity class differences. Copyright © 2012 John Wiley & Sons, Ltd.