3D analysis and grading of calcifications from ex vivo human meniscus.

OBJECTIVE: Meniscal calcifications are associated with the pathogenesis of knee osteoarthritis (OA). We propose a micro-computed tomography (µCT) based 3D analysis of meniscal calcifications ex vivo, including a new grading system. METHOD: Human medial and lateral menisci were obtained from 10 patients having total knee replacement for medial compartment OA and 10 deceased donors without knee OA (healthy references). The samples were fixed; one subsection was imaged with µCT, and the adjacent tissue was processed for histological evaluation. Calcifications were examined from the reconstructed 3D µCT images, and a new grading system was developed. To validate the grading system, meniscal calcification volumes (CVM) were quantitatively analyzed and compared between the calcification grades. Furthermore, we estimated the relationship between histopathological degeneration and the calcification severity. RESULTS: 3D µCT images depict calcifications in every sample, including diminutive calcifications that are not visible in histology. In the new grading system, starting from grade 2, each grade results in a CVM that is 20.3 times higher (95% CI 13.3-30.5) than in the previous grade. However, there was no apparent difference in CVM between grades 1 and 2. The calcification grades appear to increase with the increasing histopathological degeneration, although histopathological degeneration is also observed with small calcification grades. CONCLUSIONS: 3D µCT grading of meniscal calcifications is feasible. Interestingly, it seems that there are two patterns of degeneration in the menisci of our sample set: 1) with diminutive calcifications (calcification grades 1-2), and 2) with large to widespread calcifications (calcification grades 3-5).

The heritability of doctor-diagnosed traumatic and degenerative meniscus tears.

OBJECTIVE: To estimate the genetic contribution to traumatic and degenerative meniscus tears for men and women across the lifespan. METHODS: We linked the Swedish Twin Register with individual-level national healthcare data to form a 30-year, population-wide, longitudinal twin cohort. To study genetic contribution to meniscus tears, we estimated the heritability and familial risk using incident traumatic and degenerative tear diagnostic codes in a cohort of 88,414 monozygotic and dizygotic twin-pairs, aged ≥17 years. RESULTS: During follow-up, 3,372 (3.8%) of 88,414 twins were diagnosed with a traumatic or degenerative meniscus tear. The heritability was 0.39 (95% CI = 0.32-0.47) for men and 0.43 (95% CI = 0.36-0.50) for women, and did not vary by age. Environmental factors that were unique to each twin in a pair explained a greater proportion of the variance than genetic factors, both for men (0.61, 95% CI = 0.53-0.68) and women (0.57, 95% CI = 0.50-0.64). Separate analyses of traumatic vs degenerative meniscus tears yielded similar results. CONCLUSION: For the first time, we have estimated the genetic contribution to doctor-diagnosed meniscus tears using a twin study design. We found a relatively low to modest heritability for meniscus tears (∼40%). The heritability was also fairly stable over the lifespan, and equal in both men and women. Our findings suggest that environmental risk factors are a more important contributor to both traumatic and degenerative doctor-diagnosed meniscus tears than genetic factors.

Quantitative three-dimensional collagen orientation analysis of human meniscus posterior horn in health and osteoarthritis using micro-computed tomography.

OBJECTIVE: Knee osteoarthritis (OA) is associated with meniscal degeneration that may involve disorganization of the meniscal collagen fiber network. Our aims were to quantitatively analyze the microstructural organization of human meniscus samples in 3D using micro-computed tomography (µCT), and to compare the local microstructural organization between OA and donor samples. METHOD: We collected posterior horns of both medial and lateral human menisci from 10 end-stage medial compartment knee OA patients undergoing total knee replacement (medial & lateral OA) and 10 deceased donors without knee OA (medial & lateral donor). Posterior horns were dissected and fixed in formalin, dehydrated in ascending ethanol concentrations, treated with hexamethyldisilazane (HMDS), and imaged with µCT. We performed local orientation analysis of collagenous microstructure in 3D by calculating structure tensors from greyscale gradients within selected integration window to determine the polar angle for each voxel. RESULTS: In donor samples, meniscus bundles were aligned circumferentially around the inner border of meniscus. In medial OA menisci, the organized structure of collagen network was lost, and main orientation was shifted away from the circumferential alignment. Quantitatively, medial OA menisci had the lowest mean orientation angle compared to all groups, -24° (95%CI -31 to -18) vs medial donor and -25° (95%CI -34 to -15) vs lateral OA. CONCLUSIONS: HMDS-based µCT imaging enabled quantitative analysis of meniscal collagen fiber bundles and their orientations in 3D. In human medial OA menisci, the collagen disorganization was profound with overall lower orientation angles, suggesting collagenous microstructure disorganization as an important part of meniscus degradation.

Three-dimensional microstructure of human meniscus posterior horn in health and osteoarthritis.

OBJECTIVE: To develop and perform ex vivo 3D imaging of meniscus posterior horn microstructure using micro-computed tomography (µCT), and to compare specimens from healthy references against end-stage osteoarthritis (OA) using conventional section-based histology and qualitative µCT. DESIGN: We retrieved human medial and lateral menisci from 10 deceased donors without knee OA (healthy references) and medial and lateral menisci from 10 patients having total knee replacement for medial compartment OA. Meniscal posterior horns were dissected and fixed in formalin. One subsection underwent hexamethyldisilazane (HMDS) treatment and µCT imaging. Pauli's histopathological scoring was performed for 3 other subsections. The differences in histopathological scores were estimated using mixed linear regression, resulting in fixed effects estimates for within-knee comparisons and adjusted for age and body mass index for between-subjects comparisons. RESULTS: 3D visualization with µCT qualitatively revealed similar microstructural changes in the posterior horns as conventional histology. The mean histopathological score was higher for medial menisci from OA knees vs both medial reference menisci (mean difference [95% CI], 3.9 [2.6,5.3]), and lateral menisci from OA knees (3.9 [2.9,5.0]). The scores were similar between lateral menisci from OA knees and lateral reference menisci (0.8 [-0.6,2.2]), and between medial and lateral reference menisci (0.8 [-0.3,1.9]). CONCLUSIONS: HMDS-based µCT protocol allows unique 3D visualization of meniscus microstructures. Posterior horns of medial menisci from medial compartment OA knees had higher histopathological scores than both the lateral posterior horns from the same OA knees and medial reference menisci, suggesting a strong association between meniscus degradation and unicompartmental knee OA.

The use of videofluoroscopy (VFS) and fibreoptic endoscopic evaluation of swallowing (FEES) in the investigation of oropharyngeal dysphagia in stroke patients: A narrative review.

OBJECTIVES: Patients with suspected acute stroke require rapid assessment of swallowing on admission. If aspiration is suspected, this takes the form of specialist assessment, using either videofluoroscopy (VFS) or fibreoptic endoscopic evaluation of swallowing (FEES). The review aim was to evaluate and compare the effectiveness of each method in stroke patients. Literature was collected from the databases Scopus, Web of Science and Medline, and articles included in the review were published within the last 10 years, in the English language. KEY FINDINGS: Sensitivity and specificity ranged from 0.29-0.33 and 0.96-1.0 for VFS, respectively, and 0.37-1.0 and 0.65-0.87 for FEES, respectively, depending on the type of bolus utilised. VFS is the current gold-standard for the investigation of oropharyngeal dysphagia (OD), however, radiation dose and patient transport implications mean FEES may be preferred. FEES has limitations including 'whiteout' and the invasive nature of the endoscope. The NICE guidelines do not recommend a definitive protocol specifically in stroke patients. This suggests further research may be required to determine the most effective method. CONCLUSION: FEES is a beneficial first line examination, providing limited invasiveness, and administering a high level of patient suitability, without using ionising radiation. VFS could potentially be useful following FEES to secure full visualisation, ensuring an aspiration event is not missed during FEES. IMPLICATIONS FOR PRACTICE: Use of FEES as the first line test rather than VFS, ensures radiation dose is as low as reasonably practicable (ALARP). Ongoing research to ensure protocols follow current best practice can help ensure accurate management of oropharyngeal dysphagia in stroke patients.

Gonad shield placement accuracy in pelvic radiographs for male patients: A prospective phantom study and survey of third year undergraduate diagnostic radiography students".

INTRODUCTION: Little research has focused on the accuracy of gonad shield placement, especially by students. While studies have investigated the presence of gonad shields they do not aim to measure accuracy but only look at repeatability. This study aimed to establish students' knowledge of gonad shields and their accuracy in placing it. METHODS: Following an invitation email and informed consent, students completed a 7-question questionnaire and placed a gonad shield on a Pixi full body adult phantom (male configuration). The phantom was x-rayed and images were assessed for gonad shield positioning in terms of obscuring bony anatomy, correct orientation and distance from a "gold standard" position. RESULTS: 36% of images displayed shields covering bony anatomy while 16% of shields were incorrectly orientated. All shields incorrectly orientated also covered bony anatomy. Statistical significance was seen between incorrect shield orientation and the obscuring of bony anatomy (p = 0.01). Dispersion of positioning error measurements ranged from -6.80 mm (better placed than the "gold standard") to 62.35 mm inferiorly, with an average 28.22 mm inferiorly. CONCLUSION: The average misplacement of 28.22 mm suggests participants placed the gonad shielding lower than necessary to avoid obscuring bony anatomy. The 36% of misplaced shields, while lower than in previous studies, is still a significant number of radiographs that would require repeats. IMPLICATIONS FOR PRACTICE: Given the associated difficulties surrounding gonad shields and their placement, this study supports previous research suggesting that the benefit of using gonad shielding is questionable.

The impact of gonad shielding in anteroposterior (AP) pelvis projections in an adult: A phantom study utilising digital radiography (DR).

INTRODUCTION: Positioning relative to the lateral automatic exposure control (AEC) chambers (cranial/caudal orientation) optimises dose and image quality in pelvic radiography. In the cranial orientation introducing gonad shielding (GS) in females may increase radiation dose. The aim of this study was to fully optimise the combination of pelvis orientation and use of GS in both male and females. METHODS: An anthropomorphic pelvis phantom was exposed, with dose area product (DAP) recorded, in both orientations without GS and four conditions with GS: cranial orientation (female/male), caudal orientation (female/male). A 4 cm × 4 cm grid incorporating thirteen positions for the GS resulted in 52 experimental settings. Blind image quality assessment, utilising a modified scale, was undertaken by two experienced observers. RESULTS: Comparing no GS (caudal orientation) to female GS, no significant change in DAP was seen (3.97 v 4.03 dGy*cm2; Mann-Whitney p = 0.060). Comparing no GS (cranial orientation) to male GS no significant change in DAP was seen (8.66 v 8.77 dGy*cm2; Mann-Whitney; p = 0.210). DAP increased significantly with introduction of female GS in the cranial orientation (23%: 8.66 v 10.65 dGy*cm2, Mann-Whitney; p < 0.001) and male GS in the caudal orientation (22.8%: 3.97 v 4.87 dGy*cm2, Mann-Whitney; p < 0.001). Significantly higher repeat rates (Chi-squared test; p < 0.001) were seen for GS in female (85-100%) compared to male (30.8%). CONCLUSION: The use of gonad shielding can increase DAP and lead to repeats being required, with more required for female GS usage, suggesting the utility of GS for pelvis examinations is questionable. IMPLICATIONS FOR PRACTICE: Optimisation of radiation dose in pelvic radiographic examinations utilising AEC terminated exposures requires consideration of AEC chamber position and GS usage.

Cost-effectiveness of functional cardiac testing in the diagnosis and management of coronary artery disease: a randomised controlled trial. The CECaT trial.

OBJECTIVES: To assess the acceptability and feasibility of functional tests as a gateway to angiography for management of coronary artery disease (CAD), the ability of diagnostic strategies to identify patients who should undergo revascularisation, patient outcomes in each diagnostic strategy, and the most cost-effective diagnostic strategy for patients with suspected or known CAD. DESIGN: A rapid systematic review of economic evaluations of alternative diagnostic strategies for CAD was carried out. A pragmatic and generalisable randomised controlled trial was undertaken to assess the use of the functional cardiac tests: angiography (controls); single photon emission computed tomography (SPECT); magnetic resonance imaging (MRI); stress echocardiography. SETTING: The setting was Papworth Hospital NHS Foundation Trust, a tertiary cardiothoracic referral centre. PARTICIPANTS: Patients with suspected or known CAD and an exercise test result that required non-urgent angiography. INTERVENTIONS: Patients were randomised to one of the four initial diagnostic tests. MAIN OUTCOME MEASURES: Eighteen months post-randomisation: exercise time (modified Bruce protocol); cost-effectiveness compared with angiography (diagnosis, treatment and follow-up costs). The aim was to demonstrate equivalence in exercise time between those randomised to functional tests and those randomised to angiography [defined as the confidence interval (CI) for mean difference from angiography within 1 minute]. RESULTS: The 898 patients were randomised to angiography (n = 222), SPECT (n = 224), MRI (n = 226) or stress echo (n = 226). Initial diagnostic tests were completed successfully with unequivocal results for 98% of angiography, 94% of SPECT (p = 0.05), 78% of MRI (p < 0.001) and 90% of stress echocardiography patients (p < 0.001). Some 22% of SPECT patients, 20% of MRI patients and 25% of stress echo patients were not subsequently referred for an angiogram. Positive functional tests were confirmed by positive angiography in 83% of SPECT patients, 89% of MRI patients and 84% of stress echo patients. Negative functional tests were followed by positive angiograms in 31% of SPECT patients, 52% of MRI patients and 48% of stress echo patients tested. The proportions that had coronary artery bypass graft surgery were 10% (angiography), 11% (MRI) and 13% (SPECT and stress echo) and percutaneous coronary intervention 25% (angiography), 18% (SPECT) and 23% (MRI and stress echo). At 18 months, comparing SPECT and stress echo with angiography, a clinically significant difference in total exercise time can be ruled out. The MRI group had significantly shorter mean total exercise time of 35 seconds and the upper limit of the CI was 1.14 minutes less than in the angiography group, so a difference of at least 1 minute cannot be ruled out. At 6 months post-treatment, SPECT and angiography had equivalent mean exercise time. Compared with angiography, the MRI and stress echo groups had significantly shorter mean total exercise time of 37 and 38 seconds, respectively, and the upper limit of both CIs was 1.16 minutes, so a difference of at least 1 minute cannot be ruled out. The differences were mainly attributable to revascularised patients. There were significantly more non-fatal adverse events in the stress echo group, mostly admissions for chest pain, but no significant difference in the number of patients reporting events. Mean (95% CI) total additional costs over 18 months, compared with angiography, were 415 pounds (-310 pounds to 1084 pounds) for SPECT, 426 pounds (-247 pounds to 1088 pounds) for MRI and 821 pounds (10 pounds to 1715 pounds) for stress echocardiography, with very little difference in quality-adjusted life-years (QALYs) amongst the groups (less than 0.04 QALYs over 18 months). Cost-effectiveness was mainly influenced by test costs, clinicians' willingness to trust negative functional tests and by a small number of patients who had a particularly difficult clinical course. CONCLUSIONS: Between 20 and 25% of patients can avoid invasive testing using functional testing as a gateway to angiography, without substantial effects on outcomes. The SPECT strategy was as useful as angiography in identifying patients who should undergo revascularisation and the additional cost was not significant, in fact it would be reduced further by restricting the rest test to patients who have a positive stress test. MRI had the largest number of test failures and, in this study, had the least practical use in screening patients with suspected CAD, although it had similar outcomes to stress echo and is still an evolving technology. Stress echo patients had a 10% test failure rate, significantly shorter total exercise time and time to angina at 6 months post-treatment, and a greater number of adverse events, leading to significantly higher costs. Given the level of skill required for stress echo, it may be best to reserve this test for those who have a contraindication to SPECT and are unable or unwilling to have MRI. Further research, using blinded reassessment of functional test results and angiograms, is required to formally assess diagnostic accuracy. Longer-term cost-effectiveness analysis, and further studies of MRI and new generation computed tomography are also required.

Alternative light source (polilight) illumination with digital image analysis does not assist in determining the age of bruises.

The age of a bruise may be of interest to forensic investigators. Previous research has demonstrated that an alternative light source may assist in the visualisation of faint or non-visible bruises. This project aimed to determine if an alternative light source could be utilised to assist investigators estimate the age of a bruise. Forty braises, sustained from blunt force trauma, were examined from 30 healthy subjects. The age of the bruises ranged from 2 to 231 h (mean = 74.6, median = 69.0). Alternative light source (polilight) illumination at 415 and 450 nm was used. The black and white photographs obtained were assessed using densitometry. A statistical analysis indicated that there was no correlation between time and the mean densitometry values. The alternative light source used in this study was unable to assist in determining the age of a bruise.

Protein phosphatase 2Bw and protein phosphatase Z are Saccharomyces cerevisiae enzymes.

cDNAs encoding three protein phosphatases, termed PP2Bw (Da Cruz e Silva, E.F. and Cohen, P.T.W. (1989) Biochim. Biophys. Acta 1009, 293-296), PPZ1 and PPZ2 that have been isolated from a Clontech 'rabbit brain' library are shown to be Saccharomyces cerevisiae clones. PPZ1 and PPZ2 are two novel yeast phosphatases showing 93% amino acid sequence identity to one another. PPZ1 shows approx. 60% sequence identity to S. cerevisiae or mammalian PP1 and approx. 40% identity to S. cerevisiae or mammalian PP2A. These and other observations suggest that the two isoforms of PPZ have functions distinct from those of PP1.

Increased prevalence of mitochondrial DNA deletions in skeletal muscle of older individuals with impaired glucose tolerance: possible marker of glycemic stress.

To determine the relationship between mitochondrial DNA (mtDNA) mutations and age-related impaired glucose tolerance (IGT), mtDNA from skeletal muscle of 19 volunteers, ages 55-75 years, with either IGT or diabetes and 17 age- and sex-matched control subjects was analyzed using a long-extension polymerase chain reaction (PCR) combined with a quantitative PCR. We found the common 4,977-bp deletion in 84% of the IGT/diabetes group compared with only 41% in the control group (P < 0.02). Multiple other deletions of different sizes were identified in 13 out of 19 IGT/diabetes patients (68%) compared with 2 out of 17 control subjects (12%) (P < 0.002). Because of the heterogeneity and variation in the mutations identified, we propose that these mtDNA mutations were the result rather than the cause of IGT. The increase in type and frequency of mtDNA deletions in diabetes and IGT patients may be related to oxidative damage by oxygen free radicals. These may be produced in greater amounts as a result of hyperglycemia or may be more abundant because of an abnormality in the scavenging of free radicals by antioxidants.

Isolated ductus arteriosus aneurysm in the fetus and infant: a multi-institutional experience.

OBJECTIVES: The purpose of this study was to describe the clinical characteristics and outcome and to elucidate the pathogenesis of ductus arteriosus aneurysm (DAA). BACKGROUND: Ductus arteriosus aneurysm is a rare lesion that can be associated with severe complications including thromboembolism, rupture and death. METHOD: We reviewed the clinical records, diagnostic imaging studies and available histology of 24 cases of DAA, diagnosed postnatally (PD) in 15 and antenatally (AD) in 9 encountered in five institutions. RESULTS: Of PD cases, 13 presented at <2 months, and all AD cases were detected incidentally after 33 weeks of gestation during a late trimester fetal ultrasound study. Of the 24, only 4 had DAA-related symptoms and 6 had associated syndromes: Marfan, Smith-Lemli-Opitz, trisomies 21 and 13 and one possible Ehlers-Danlos. Three had complications related to the DAA: thrombus extension into the pulmonary artery, spontaneous rupture, and asymptomatic cerebral infarction. Six underwent uncomplicated DAA resection for ductal patency, DAA size or extension of thrombus. In the four examined, there was histologic evidence of reduced intimal cushions in two and abnormal elastin expression in two. Five of the 24 died, with only one death due to DAA. Of 19 survivors, all but one remain clinically asymptomatic at a median follow-up of 35 months; however, two have developed other cardiac lesions that suggest Marfan syndrome. A review of 200 consecutive third trimester fetal ultrasounds suggests an incidence of DAA of 1.5%. CONCLUSIONS: Ductus arteriosus aneurysm likely develops in the third trimester perhaps due to abnormal intimal cushion formation or elastin expression. Although it can be associated with syndromes and severe complications, many affected infants have a benign course. Given the potential for development of other cardiac lesions associated with connective tissue disease, follow-up is warranted.

AIDS risk-taking behavior during carnival in São Paulo, Brazil.

OBJECTIVE: The Brazilian Carnival is thought to be a time when the risk of HIV infection is likely to be high. We therefore compared the risk during Carnival to risk in the past month among male samba school participants in São Paulo, Brazil. SUBJECTS AND METHODS: A cross-sectional study was conducted among 380 male samba school drummers randomly sampled during rehearsal for the 1993 Carnival in São Paulo by means of a 20-min interviewer-administered questionnaire. The main outcome variable was condom use with non-steady partners. RESULTS: The sexual behavior of 36.1% of subjects risked HIV infection, but only 9.7% of all subjects were at risk only during Carnival. Subjects with a sexual risk of HIV differed from those without risk in substance use, attitudes towards condoms and expectations about Carnival; those who were at risk only during Carnival did not differ from those who were at risk at other times. About half of the subjects had been given free condoms during Carnival, although few of the men at risk had actually used them. CONCLUSIONS: Though more than a third of the drummers were at risk of HIV infection, only a small per cent were at risk only during Carnival. The level of sexual risk of HIV infection is probably better explained by factors in the men's daily lives, rather than through information on risks taken during Carnival. These results raise questions concerning the efficacy of universal condom distribution during Carnival, since about half of the men were given condoms but few of those at risk actually used them. A targeted distribution of condoms to populations with a high demonstrated risk may be more effective in preventing new HIV infection.

Socioeconomic status and risk of HIV-1, syphilis and hepatitis B infection among sex workers in São Paulo State, Brazil. Instituto Adolfo Lutz Study Group.

OBJECTIVES: To determine how HIV risk behavior and the prevalences of sexually transmitted diseases vary according to socioeconomic status and city among sex workers in São Paulo State, Brazil. SUBJECTS AND METHODS: A cross-sectional study of 600 female sex workers (100 of a higher socioeconomic status and 100 of a lower socioeconomic status in each city) was conducted in the cities of São Paulo, Campinas and Santos. HIV risk behavior was assessed by questionnaire; serological tests were administered to assess prior exposure to HIV-1, syphilis and hepatitis B. RESULTS: Only statistically significant (P < 0.05) findings are reported here. Compared to those with a higher socioeconomic status, sex workers with a lower socioeconomic status worked longer hours each day (9.6 versus 7.9), had more clients per day (5.4 versus 2.6) and had fewer episodes of intercourse per client per encounter (1.1 versus 1.4). Levels of condom use for vaginal, anal and oral sex were significantly higher in Santos than in São Paulo or Campinas. Twenty-three per cent of the women said they feared violence if they insisted that their clients wear condoms; 74% voiced similar fears regarding their non-client sexual partners. Overall, 11% of sex workers were positive for exposure to HIV-1, 45% for syphilis and 39% for hepatitis B. Those with a lower socioeconomic status were more likely than those with a higher socioeconomic status to be infected with HIV-1 (17 versus 4%), syphilis (66 versus 24%) and hepatitis B (52 versus 26%), but there were no differences in prevalence rates by city. CONCLUSIONS: These data demonstrate substantial heterogeneity in HIV risk behavior and the prevalence of HIV-1 and other sexually transmitted diseases among sex workers in São Paulo State, many of which were related to differences in socioeconomic status. Interventions to prevent HIV transmission among sex workers must be tailored to the local environment and, in particular, to the socioeconomic status of these workers.

Protein serine/threonine phosphatases; an expanding family.

Five protein serine/threonine phosphatases (PP) have been identified by cloning cDNA from mammalian and Drosophila libraries. These novel enzymes, which have not yet been detected by the techniques of protein chemistry and enzymology, are termed PPV, PP2Bw, PPX, PPY and PPZ. The complete amino acid sequences of PPX, PPY and PPZ and an almost complete sequence of PPV are presented. In the catalytic domain PPV and PPX are more similar to PP2A (57-69% identity) than PP1 (45-49% identity), while PPY and PPZ are more similar to PP1 (66-68% identity) than PP2A (44% identity). The cDNA for PP2Bw encodes a novel Ca2+/calmodulin-dependent protein phosphatase only 62% identical to PP2B in the catalytic domain. Approaches for determining the cellular functions of these protein phosphatases are discussed.

Dietary carbohydrates and endurance exercise.

Antecedent diet can greatly influence both substrate utilization during exercise and exercise performance itself. A number of studies have convincingly demonstrated that short-term (three to seven days) adaptation to a low carbohydrate diet results in greatly reduced liver and muscle glycogen stores. While carbohydrate utilization after such a diet is reduced, the limited glycogen stores can severely limit endurance exercise performance. High carbohydrate diets on the other hand expand carbohydrate stores which can limit performance. However, long-term adaptation to a low carbohydrate diet can greatly alter muscle and whole body energy metabolism to drastically limit the oxidation of limited carbohydrate stores with no adverse effect on performance. Glycogen loading techniques can result in supercompensation of muscle stores. Exercise induced depletion of muscle glycogen is the most important single factor in this phenomenon. Following the exercise a low carbohydrate diet for two to three days after which a high carbohydrate diet is eaten seemingly has the same effect on increasing muscle glycogen stores as simply eating a high carbohydrate diet. The form of the dietary carbohydrate during glycogen loading should be high in complex carbohydrates; however, the type of dietary starch that effects the greatest rate of resynthesis has not been investigated. Rapid resynthesis of glycogen following exercise is at least in part due to increased insulin sensitivity. The enhanced glucose transport caused by the increased sensitivity provides substrate for glycogen synthase. How rapidly this enhanced sensitivity returns to pre-exercise levels in humans is uncertain.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of calcium carbonate and hydroxyapatite on zinc and iron retention in postmenopausal women.

We measured the effect of calcium carbonate and hydroxyapatite on whole-body retention of zinc-65 in 11 and iron-59 in 13 healthy, postmenopausal women. In a single-blind, controlled, crossover study, each subject, on three occasions, ingested a standard test meal supplemented with iron-59 or zinc-65 and capsules containing placebo or 500 mg elemental calcium as calcium carbonate or hydroxyapatite. Whole-body countings were performed prior to, 30 min after, and 2 wk after each meal. Mean (SEM) zinc retention was 18.1 +/- 1.0% with placebo (control) and did not vary significantly with calcium carbonate (110.0 +/- 8.6% of control) or hydroxyapatite (106.0 +/- 7.9% of control). Iron retention, 6.3 +/- 2.0% with placebo, was significantly reduced with both calcium carbonate (43.3 +/- 8.8% of control, p = 0.002) and hydroxyapatite (45.9 +/- 10.0% of control, p = 0.003). Iron absorption may be significantly reduced when calcium supplements are taken with meals.

Lipoprotein response to exercise training and a low-fat diet in older subjects with glucose intolerance.

The purpose of this study was to determine the effect of aerobic exercise training (Ex), a low-fat diet (LF, 19% fat), or combined interventions (LF-Ex) on lipoprotein cholesterol (LDL, HDL, and VLDL) and triglyceride (TG) concentrations in glucose-intolerant subjects while their weight was maintained. Baseline dietary fat and carbohydrate composition, body composition, body mass index, age, and lipoprotein cholesterol were not different among groups. Aerobic capacity increased in both exercise groups (P < 0.01) and remained unchanged in the LF group. Body composition was unaltered and change in body weight (kg) was small: Ex, -0.8 +/- 0.4, (P < 0.05); LF, +0.4 +/- 0.4; (NS); LF-Ex, -1.4 +/- 0.4 (P < 0.01). Exercise alone did not significantly affect lipoprotein cholesterol or TG concentrations. In LF and LF-Ex, respectively, decreases (P < 0.02) in total cholesterol (-0.66 +/- 0.24 and -0.42 +/- 0.21 mmol/L), HDL (-0.14 +/- 0.07 and -0.26 +/- 0.04), and LDL (-0.60 +/- 0.25 and -0.23 +/- 0.13) were seen after 12 wk, whereas VLDL and TG remained unchanged. Our data indicate that beneficial effects of exercise training on lipid indexes are not observed in subjects with impaired glucose tolerance on either an average US diet or a low-fat diet if substantial changes in weight or body composition do not occur.

Long-term effects of a high-carbohydrate diet and exercise on insulin action in older subjects with impaired glucose tolerance.

Carbohydrate metabolism was assessed in 20 glucose-intolerant subjects before and after 12 wk on a high-carbohydrate diet (HC) or the diet combined with exercise training (HC-EX). The diet provided 60% of energy as carbohydrate and 20% as fat. Neither treatment altered fasting glucose or insulin concentrations or their response to a meal. During a glucose clamp (216 pmol insulin/L) glucose disposal increased from 13.2 +/- 0.83 to 14.6 +/- 0.83 mumol.kg fat-free mass-1.min-1 (P < 0.05) in both groups. During more pronounced hyperinsulinemia (654 pmol/L) glucose disposal did not change significantly (49.9 +/- 3.8 to 50.7 +/- 3.8 mumol.kg fat-free mass-1.min-1). Muscle glycogen increased in the HC-EX group (78.5 +/- 8.1 to 161.1 +/- 15.7 mmol glucose/kg muscle), with no changes in the HC group. These results do not support the recommendation to increase the dietary carbohydrate content for improving postprandial glucose metabolism or insulin action in glucose-intolerant adults unless combined with exercise training, which promotes muscle glycogen storage.

Monitoring eosinophil activation and liver function after liver transplantation.

BACKGROUND: Portal tract eosinophil infiltration and an increase in the blood eosinophil count (EOS) have been shown to be specific markers of liver allograft rejection. The graft eosinophil infiltration is associated with the local release of eosinophil cationic protein. Therefore, serum eosinophil cationic protein concentration (ECP) is a potential marker for acute allograft rejection. We investigated the chronological relationship among and diagnostic value of serial changes in EOS, ECP, and liver function tests (LFTs) following liver transplantation. METHODS: EOS, ECP, serum alpha-glutathione S-transferase concentration, and conventional LFTs were measured in serial samples collected over the first 3 postoperative months following 58 liver transplants. The diagnostic potential of each test, alone or in combination, was reviewed over the entire follow-up period. RESULTS: EOS and ECP increased at a median period of 3.5 and 4 days, respectively, before the diagnosis of acute rejection, and this increase was significantly earlier than the corresponding changes in LFTs (P<0.05). There was a significant correlation between the day of the first increase in EOS and alpha-glutathione S-transferase (rs=0.535; P=0.009) and EOS and alanine transaminase (rs=0.629; P=0.004). The optimum combination of tests for the diagnosis of acute rejection was an increase in both EOS and GST with a predictive efficiency of 84%. CONCLUSIONS: Increases in EOS and ECP are early indicators of acute liver allograft rejection and precede evidence of hepatocellular damage. However, an increase in ECP was also frequently associated with infection. Therefore, we recommend the regular monitoring of EOS in conjunction with routine LFTs after liver transplantation as an aid to the early diagnosis of acute rejection.