Oxidation-reduction properties of methylglyoxal-modified protein in relation to free radical generation

Oxidation-reduction properties of methylglyoxal-modified protein in relation to free radical generation were investigated. Glycation of bovine serum albumin by methylglyoxal generated the protein-bound free radical, probably the cation radical of the cross-linked Schiff base, as observed in the reaction of methylglyoxal with L-alanine (Yim, H.-S., Kang, S.-O., Hah, Y. C., Chock, P. B., and Yim, M. B. (1995) J. Biol. Chem. 270, 28228-28233) or with Nalpha-acetyl-L-lysine. The glycated bovine serum albumin showed increased electrophoretic mobility suggesting that the basic residues, such as lysine, were modified by methylglyoxal. The glycated protein reduced ferricytochrome c to ferrocytochrome c in the absence of oxygen or added metal ions. This reduction of cytochrome c was accompanied by a large increase in the amplitude of the electron paramagnetic resonance signal originated from the protein-bound free radical. In addition, the glycated protein catalyzed the oxidation of ascorbate in the presence of oxygen, whereas the protein free radical signal disappeared. These results indicate that glycation of protein generates active centers for catalyzing one-electron oxidation-reduction reactions. This active center, which exhibits enzyme-like characteristic, was suggested to be the cross-linked Schiff base/the cross-linked Schiff base radical cation of the protein. It mimics the characteristics of the metal-catalyzed oxidation system. The glycated bovine serum albumin cross-linked further to the cytochrome c in the absence of methylglyoxal. The cross-linked cytochrome c maintains its oxidation-reduction properties. These results together indicate that glycated proteins accumulated in vivo provide stable active sites for catalyzing the formation of free radicals.     

Iron status, menarche, and calcium supplementation in adolescent girls

The effects of growth, menstrual status, and calcium supplementation on iron status were studied over 4 y in 354 girls in pubertal stage 2 who were premenarcheal at baseline (x+/-SD age: 10.8+/-0.8 y). Girls were randomly assigned to placebo or treatment with 1000 mg Ca/d as calcium citrate malate. Anthropometric characteristics, bone mass, and nutritional status were measured biannually; ferritin was measured annually; and red blood cell indexes were determined at 4 y. The simultaneous effects of iron intake and menstrual status on serum ferritin, after change in lean body mass (LBM) was controlled for, were evaluated in subjects in the upper and lower quartiles of cumulative iron intake. The average maximal accumulation of LBM (386 g/mo; 95% CI: 372, 399) occurred 0.5 y before the onset of menarche. Change in LBM was a significant predictor of serum ferritin (P < 0.0001), with a negative influence on iron status (t ratio=-4.12). The 2 fitted mathematical models representing ferritin concentrations of subjects in the upper and lower quartiles of cumulative iron intake were significantly different (P < 0.018). The regression line of the ferritin concentration in menstruating girls with high iron intakes had a less negative slope than the line fit to serum ferritin concentrations in girls with low iron intakes (NS). Serum ferritin concentrations at 0, 1, 2, 3, and 4 y were not significantly different between groups. In addition, there was no significant difference between groups in any of the red blood cell indexes. In summary, growth spurt and menstrual status had adverse effects on iron stores in adolescent girls with low iron intakes (<9 mg/d), whereas long-term supplementation with calcium (total intake: approximately 1500 mg/d) did not affect iron status.     

Decision-theoretic case-based reasoning

We describe a decision-theoretic methodology for case-based reasoning in diagnosis and troubleshooting applications. The system utilizes a special-structure Bayesian network to represent diagnostic cases, with nodes representing issues, causes, and symptoms. Dirichlet distributions are assessed at knowledge acquisition time to indicate the strength of relationships between variables. During a diagnosis session, a relevant subnetwork is extracted from a Bayesian-network database that describes a very large number of diagnostic interactions and cases. The constructed network is used to make recommendations regarding possible repairs and additional observations, based on an estimate of expected repair costs. As cases are resolved, observations of issues, causes, symptoms, and the success of repairs are recorded. New variables are added to the database, and the probabilities associated with variables already in the database are updated. In this way, the inferential behavior of system adjusts to the characteristics of the target population of users. We show how these elements work together in a cycle of troubleshooting tasks, and describe some results from a pilot system implementation and deployment     

Reflection measurement during retinal laser coagulation in patients. Development of an automatically controlled dosimeter

PURPOSE: Retinal laser coagulation has limited reproducibility, because every laser exposition is unpredictably affected by pigmentation and media opacities. This can lead to complications. A feedback-controlled dosimeter would make retinal laser treatment a safer, more reproducible and faster procedure. METHOD: A reflectometer was developed that allows monitoring of the reflection of laser light during standard photocoagulation. Hundreds of coagulations in rabbit eyes and about 12,000 coagulations in patients undergoing routine laser treatment were recorded. RESULTS: The results of the first reflectance measurements in humans are presented along with extensive animal studies. A typical reflectance history was found for different lesion intensities. The degree of retinal whitening correlates with reflectance characteristics. These characteristics allow an early prediction of lesion intensity. Motion during laser exposure affects each coagulation in a fashion similar to spot size and exposure time. CONCLUSION: Reflectometry is the currently most effective means of monitoring lesion development. An automatic dosimeter for retinal photocoagulation seems feasible.     

A nursing rehabilitation program for women with breast cancer receiving adjuvant chemotherapy

PURPOSE/OBJECTIVES: To examine the effects of a comprehensive rehabilitation program on facilitating physical and psychosocial adaptation of women with breast cancer who are receiving adjuvant chemotherapy. DESIGN: Experimental. SETTING: Breast evaluation clinics of two New England medical centers with comprehensive cancer treatment programs. SAMPLE: 14 women (mean age = 44 years) receiving adjuvant chemotherapy for breast cancer (86% stage II) following surgical treatment. METHODS: Subjects were assigned randomly to the experimental group or the usual care group. Experimental group members began a structured exercise program of walking and attended support group meetings. All subjects were tested before beginning chemotherapy, during the course of chemotherapy, and one month following chemotherapy completion. MAIN RESEARCH VARIABLES: Performance status, physical functioning, psychosocial adjustment, self-concept and body image, and 12 symptoms (e.g., fatigue, nausea, anxiety). FINDINGS: Measures of physical performance, psychosocial adjustment, and symptom intensity revealed improved adaptation in subjects who completed the walking/support group program. CONCLUSIONS: Physical and psychosocial benefits from a modest walking exercise program and a support group are possible for patients receiving adjuvant chemotherapy. IMPLICATIONS FOR NURSING PRACTICE: Although more detailed research is necessary to answer some of the questions raised by this study, implementing the walking program and forming a support group are achievable in an outpatient setting.     

External Quality Assessment of Microbial Counts from Water: To Score or Not to Score for Proficiency

Scoring schemes were first introduced in water-chemistry inter-laboratory proficiency tests. Such scoring does not behave in a comparable manner when applied to microbiology external quality assessment. Conventional scores can become a lottery. This poses a challenge to (a) find helpful statistical methods which will look beyond this natural variation and (b) attempt to identify any poor performance by the participants. The aim is to provide useful management tools.
In the Public Health Laboratory Service, water external quality assessment scheme participants have detected methodology problems. Formal analyses are carried out on cumulated results in two stages, first demonstrating whether there is any systematic difference between laboratories of microbiological as well as statistical significance and only then allocating participants to categories of acceptable, or poor, performance. The scheme has been operating for several years and performance improvements are evident.     

Frequency-shaped amplification changes the neural representation of speech with noise-induced hearing loss

Apoptosis is a mode of active cell death. We have examined whether 2-chloroethylethyl sulfide (CEES), a sulfur vesicating agent, triggers apoptosis as a cytotoxic mechanism. Incubation of thymocytes with CEES, resulted in an induction of apoptotic features of cell death. Treatment of cells with 100 microM CEES for 5 h increased DNA fragmentation to approximately 40% of control. The fragmentation of DNA was visualized by agarose gel electrophoresis. It showed ladder pattern of DNA fragmentation, which indicates internucleosomal cleavage of DNA. Further evidence of apoptosis was observed in morphological changes of nuclei by using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. The percentage of TUNEL positive cells was dependent upon CEES concentrations. CEES induced the classical morphological features of apoptosis in nucleus. These features were accompanied by condensation of chromatin, which arranged in sharply declined clumps and fragmentation of nucleus. To study requirement for synthesis of new protein in CEES-induced apoptosis, we studied the effect of cycloheximide for apoptotic activity. This protein synthesis inhibitor did not suppress the CEES-induced apoptotic activity. Taken together, these results suggest that CEES-induced apoptosis as a cytotoxicmechanism and this process occurs independent of synthesis of new protein.     

Benefits realisation management: Panacea or false dawn?

Benefits Realisation Management (BRM) is becoming an increasingly important aspect of project and programme management. However, commentators have observed that the practice of BRM is often flawed, and have made suggestions as to how practice might be improved. This paper is concerned with the reasons why the implementation of BRM might not be straightforward, by focusing on the underlying assumptions. It will approach the issue by drawing on the author's experience from the 1990s and 2000s in working in the management of government-funded regeneration programmes in the UK. In this field there was a rigid benefits management framework, although it precedes the development of BRM. The paper will argue that there are important underlying conceptual issues in benefits management which have practical implications and need to be recognised in the development of theory for BRM.     

Thymus size in infants from birth until 24 months of age evaluated by ultrasound. A longitudinal prediction model for the thymic index

To determine whether an absence of leukocytes in semen and urine predicts an absence of Chlamydia trachomatis in asymptomatic infertile men, chlamydial DNA was detected in subjects' semen and urine by ligase chain reaction (LCR). Ninety-eight infertile men were studied, including 39 cases of oligozoospermia, 19 of azoospermia, 16 of asthenozoospermia, and 24 of normozoospermia. None of the subjects had pyospermia or pyuria. C. trachomatis was detected by LCR. Antichlamydial and antisperm antibody were also measured. C. trachomatis was detected by LCR in the semen of only 1 of 98 patients (1.02%), but not in the urine samples. In C. trachomatis-positive patients LCR, IgG, and IgA levels were higher than normal. No antisperm antibody was detected. Even if leukocytes are not observed in the semen and urine of asymptomatic infertile men, the presence of C. trachomatis in semen specimens is rarely observed. Therefore, it should be noted that the presence of C. trachomatis in such cases is addressed in the context of artificial insemination and other assisted reproductive technologies.     

Carotid restenosis: operative and endovascular management

PURPOSE: Surgical management of carotid restenosis (CR) after carotid endarterectomy (CEA) has been associated with a higher perioperative complication rate than that of primary CEA. We recently used carotid angioplasty-stenting (CAS) as an alternative to operative management in patients who had undergone CEA within three years, and we retrospectively compared these results with those of operative management of CR and the overall results of CEA. METHODS: CEA was performed on 1065 adult patients (58% symptomatic, 42% asymptomatic), 62% of whom were men (n = 660) and 38% of whom were women (n = 405), from 1989 to 1997. Before our initiation of a program of CAS, 16 operative procedures (1.9% of CEAs) were performed for CR in 14 adult patients (7 women and 7 men). During the last 20 months, CAS was used in the management of 17 CRs (16 patients; 9 women and 7 men). RESULTS: The 30-day stroke morbidity-death rate for all CEAs (n = 1065) was 1.4%; 11 strokes (1. 0%) occurred (4 major strokes with disability and 7 strokes with minor or no disability), and 4 deaths (0.4%) occurred (2 deaths caused by myocardial infarction, 1 caused by intracranial hemorrhage, and 1 caused by stroke). Operative management of CR (n = 16) included patch angioplasty in 12 cases (autologous vein patches in 10 cases and synthetic patches in 2 cases), whereas interposition grafting was used in 4 cases (saphenous vein in 3 instances and synthetic [polytetrafluoroethylene] in one case). No strokes or deaths were observed. One recurrent laryngeal nerve palsy occurred (6.2%). Among the 16 patients undergoing 17 CAS procedures, the technical procedures were accomplished in all patients. No strokes or deaths occurred. No recurrent restenoses (50% or greater) have been identified within or adjacent to the CAS procedures. CONCLUSION: CR caused by myointimal hyperplasia can be managed by operative techniques or CAS with comparable periprocedural complications. Although long-term follow-up will be required to determine the incidence of recurrent restenosis, CAS may become the preferred procedure in these cases. A randomized clinical trial ultimately will be necessary to determine the role of CAS, as compared with that of operative management.