Imaging in chronic achilles tendinopathy: a comparison of ultrasonography,magnetic resonance imaging and surgical findings in 27 histologically verified cases

 Objective. To compare information gained by ultrasonography and magnetic resonance imaging (MRI) in chronic achilles tendinopathy with regard to the nature and severity of the lesion. Design. Imaging of both achilles tendons with ultrasonography and MRI was performed prior to unilateral surgery. Operative findings and histological biopsies together served as a reference. Patients. Twenty-seven patients (22 men, 5 women; mean age 44 years; 21 athletes) suffering from chronic achilles tendinopathy participated in the study. Eighteen patients had unilateral and 9 had bilateral symptoms. Results and conclusions. Surgical findings included 4 partial ruptures, 21 degenerative lesions and 2 macroscopically normal cases. Microscopy revealed tendinosis (degeneration) in all tendon biopsies, including cases with a partial rupture, but only slight changes in the paratendinous tissues (paratenon). Ultrasonography was positive in 21 of 26 and MRI in 26 of 27 cases. Severe intratendinous abnormalities and a sagittal tendon diameter >10 mm suggested a partial rupture. In tendons with a false negative result histopathological changes were mild and a tendency towards a better clinical outcome was noted in the sonographic cases. Assessment of the paratenon was unreliable with both methods. Ultrasonography and MRI give similar information and may have their greatest potential as prognostic instruments.     

Increase in the plasma concentration of free tryptophan caused by probenecid in humans

Probenecid was administered orally in a dose of 1 g twice daily for 3 days to eight patients nutriated through a gastric tube with a standarized diet containing a known amount of tryptophan. Probenecid caused an increase by 52% (P<0.01) in the free (non protein-bound) concentration of tryptophan in plasma (from 1.22±0.16 to 1.86±0,28 g/ml; mean±SEM). The total (free + protein-bound) plasma tryptophan concentration was not significantly changed by the present dose of probenecid. There was a positive correlation (Spearmans rank correlation coefficient =0.74; P<0.05) between the increase in percentage free tryptophan and the achieved plasma concentration of probenecid. The cerebrospinal fluid (CSF) concentration of tryptophan was not significantly changed by probenecid (2 g/day during 21/2 days) given to another group of five patients.It is concluded from the present study, that the increase in the CSF concentration of 5-hydroxyindoleacetic acid (5-HIAA) caused by probenecid, in addition to blockade of the 5-HIAA transport out of the CSF, might be explained by an increased rate of synthesis of brain serotonin since the availability of its precursor is increased due to the probenecid-induced increase in the plasma concentration of free tryptophan.     

Monitoring Public Health Nutrition in Europe: nutritional indicators and determinants of health status

Public Health Nutrition (PHN) focuses on the promotion of good health through healthy food habits, a physically active lifestyle and the prevention of related illness in the population. Monitoring PHN in Europe has been a project within the European Health Monitoring System (HMS), currently under development by the EU Commission within the Health Information Strand of the Public Health Programme 2003–2008. The project aims were to: (1) develop a theoretical framework for the selection and prioritization of indicators; (2) identify indicators relevant to the monitoring; (3) examine the nutritional aspects and proposals from other monitoring projects; (4) consider other novel proposals; (5) integrate these into a recommended list of indicators; (6) integrate the surveillance system into training and educational systems, in particular the Program for the European Masters in PHN. Seven main categories for investigation were identified: health promotion; food and nutrient intake, including breastfeeding and alcohol; nutritional status, physical activity habits and fitness; sociodemographic factors; inequality. Three working parties provided useful comments on the prioritizing of the many indicators. These comments were then fed to the coordinators in the Executive Committee, who further developed a prioritization scheme and produced the list of recommended indicators. The Report Committee took responsibility for preparing the report. Meanwhile experience was presented and discussed at several international meetings. The information was finally transferred to the coordinator project, the ECHI (European Core Health Indicator) project, for inclusion of relevant indicators in the ECHI lists. Information was also disseminated through publications and newsletters, and through training at the Masters and PhD levels across Europe. In most cases, operational measures could be defined in detail from their generic indicators. Standardized methods for data collection were also given. In future, we recommend that all European countries, and/or the HMS, should add questions to their surveys, according to the list of recommended indicators, to ensure that all the relevant areas of PHN are covered.     

Spontaneous resolution of high grade infantile vesicoureteral reflux

PURPOSE: We studied the spontaneous resolution rate in a group of infants with high grade vesicoureteral reflux (VUR). The influence of gender, prenatal or postnatal diagnosis, recurrent urinary tract infections (UTIs) and bladder dysfunction on the resolution rate was also evaluated. MATERIALS AND METHODS: This prospective study comprised 115 infants (80 boys and 35 girls) with high grade VUR (grades III to V). Bilateral reflux was seen in 70% of cases. The majority of patients (71%) were diagnosed after UTI during infancy and only 26% were prenatally diagnosed. Median age at diagnosis was 2.7 months. Patients were followed according to a program of repeat video cystometry and noninvasive 4-hour voiding observations. Median followup was 39 months. RESULTS: The overall spontaneous resolution rate to grade II or less for all grades was 39% with no difference between boys and girls. However, when comparing the more severe grades IV and V, we found a significantly higher resolution rate in boys during the infant year. No difference in VUR disappearance could be detected when comparing the groups according to presentation, prenatal ultrasound or pyelonephritis. Breakthrough UTIs were seen in 47% of cases despite antibacterial prophylaxis and they significantly correlated with VUR nonresolution. Bladder dysfunction was found in 37% of patients and it also significantly correlated with nonresolution. CONCLUSIONS: The spontaneous resolution rate for high grade (grades IV and V) congenital VUR was high in boys during the infant year (29%), whereas in girls and boys after the infant year the resolution rate was 9% yearly during followup. Negative prognostic factors for resolution were recurrent UTIs and bladder dysfunction.     

Body movement and physical activity energy expenditure in children and adolescents: how to adjust for differences in body size and age

BACKGROUND: Physical activity data in children and adolescents who differ in body size and age are influenced by whether physical activity is expressed in terms of body movement or energy expenditure. OBJECTIVE: We examined whether physical activity expressed as body movement (ie, accelerometer counts) differs from physical activity energy expenditure (PAEE) as a function of body size and age. DESIGN: This was a cross-sectional study in children [n = 26; (+/-SD) age: 9.6 +/- 0.3 y] and adolescents (n = 25; age: 17.6 +/- 1.5 y) in which body movement and total energy expenditure (TEE) were simultaneously measured with the use of accelerometry and the doubly labeled water method, respectively. PAEE was expressed as 1) unadjusted PAEE [TEE minus resting energy expenditure (REE); in MJ/d], 2) PAEE adjusted for body weight (BW) (PAEE. kg(-1). d(-1)), 3) PAEE adjusted for fat-free mass (FFM) (PAEE. kg FFM(-1). d(-1)), and 4) the physical activity level (PAL = TEE/REE). RESULTS: Body movement was significantly higher (P = 0.03) in children than in adolescents. Similarly, when PAEE was normalized for differences in BW or FFM, it was significantly higher in children than in adolescents (P = 0.03). In contrast, unadjusted PAEE and PAL were significantly higher in adolescents (P < 0.01). CONCLUSIONS: PAEE should be normalized for BW or FFM for comparison of physical activity between children and adolescents who differ in body size and age. Adjusting PAEE for FFM removes the confounding effect of sex, and therefore FFM may be the most appropriate body-composition variable for normalization of PAEE. Unadjusted PAEE and PAL depend on body size.     

Mothers' education but not fathers' education,household assets or land ownership is the best predictor of child health inequalities in rural Uganda

Background  

Health and nutrition inequality is a result of a complex web of factors that include socio-economic inequalities. Various socio-economic indicators exist however some do not accurately predict inequalities in children. Others are not intervention feasible.     

HER2 expression in breast cancer primary tumours and corresponding metastases. Original data and literature review

The aim of this study was to evaluate whether the HER2 expression in breast cancer is retained in metastases. The HER2 expression in primary tumours and the corresponding lymph node metastases were evaluated in parallel samples from 47 patients. The HercepTest was used for immunohistochemical analyses of HER2 overexpression in all cases. CISH/FISH was used for analysis of gene amplification in some cases. HER2 overexpression (HER2-scores 2+ or 3+) was found in 55% of both the primary tumours and of the lymph node metastases. There were only small changes in the HER2-scores; six from 1+ to 0 and one from 3+ to 2+ when the metastases were compared to the corresponding primary tumours. However, there were no cases with drastic changes in HER2 expression between the primary tumours and the corresponding lymph node metastases. The literature was reviewed for similar investigations, and it is concluded that breast cancer lymph node metastases generally overexpress HER2 to the same extent as the corresponding primary tumours. This also seems to be the case when distant metastases are considered. It has been noted that not all patients with HER2 overexpression respond to HER2-targeted Trastuzumab treatment. The stability in HER2 expression is encouraging for efforts to develop complementary forms of therapy, for example, therapy with radionuclide-labelled Trastuzumab.     

Maternal anxiety in late pregnancy: effect on fetal movements and fetal heart rate

AIM: To determine whether maternal state and trait anxiety levels affect fetal movements or fetal heart rate (FHR) in the third trimester. SUBJECTS: Forty-one healthy pregnant nulliparous women not on medication and with a singleton pregnancy. STUDY DESIGN: Maternal anxiety was assessed using the Spielberger State- Trait Anxiety Inventory (Form Y) at 36 gestational weeks. The fetuses of the women were examined at 37-40 gestational weeks with ultrasound observation of fetal movements and cardiotocography (CTG). The results of the fetal examinations were compared between women with low and high anxiety scores (low scores being defined as scores below the median and high scores as scores equal to or above the median of the study population), and correlation analyses between anxiety scores and the outcome variables were performed. OUTCOME MEASURES: The presence and duration (expressed as a percentage of the total examination time) of FHR patterns A, B, C, and D, the percentage duration of fetal movements in each FHR pattern, baseline FHR and FHR variability in each FHR pattern. RESULTS: The presence of FHR patterns A, B, C, and D, the duration of FHR patterns A, B, and C, FHR variability in FHR patterns A, B, and C, baseline FHR and the percentage duration of fetal movements in each FHR pattern did not differ between women with low and high state and trait anxiety scores. In fetuses with FHR pattern D, the duration of FHR pattern D increased with increasing maternal trait anxiety scores, (rho=0.88; p=0.008), and FHR variability in FHR pattern D increased with maternal state and trait anxiety scores (r=0.86, p=0.01; r=0.96, p=0.001). CONCLUSION: Maternal anxiety does not seem to affect fetal movements or baseline FHR in late pregnancy, but there is a possible association between maternal anxiety and the duration of FHR pattern D and FHR variability in FHR pattern D.     

Recombinant factor VIII SQ--stability of VIII: C in homogenates from porcine, monkey and human subcutaneous tissue

The aim of this paper was to investigate whether a formulation-based approach to understanding and addressing stability could generate a subcutaneous factor VIII preparation for patients as an alternative to the existing intravenous products. The low bioavailability of subcutaneously administered factor VIII could have several causes: proteolytic degradation of the protein in the interstitium; adsorption to tissue, in particular to acidic phospholipids such as L-alpha phosphatidyl-L-serine (phosphatidylserine); the absence of free von Willebrand factor in the interstitium; phagocytosis by macrophages in the interstitium or in the lymph nodes; and coagulation could be initiated upon injection. This study was undertaken to investigate the first three factors in-vitro (i.e., proteolytic degradation, adsorption to tissue and the protective effect of von Willebrand factor). The influence of some other macromolecular stabilisers and protease inhibitors was also investigated. The stability of factor VIII activity (VIII: C) was investigated in homogenates from porcine, monkey and human subcutaneous tissue. Possible coagulation was prevented in these studies by the presence of both citrate and antithrombin. An exploratory in-vivo study was performed in the pig; plasma samples were assayed with a factor VIII:Ag (90kDa) ELISA. The decrease in VIII:C appeared to be more pronounced in homogenates from monkey and human tissues than in porcine homogenate. The results from human tissue homogenate resembled the degradation profile seen in monkey homogenate. Both the von Willebrand factor and phosphatidylserine/phosphatidylcholine (PS/PC) liposomes showed a significant stabilising effect on VIII:C in the tissue homogenates. The qualitative pattern was similar in porcine, monkey and human tissue. A combination of several protease inhibitors seemed to have a protective effect on the stability of VIII: C albeit at high concentrations of inhibitors and the effect was less than that of PS/PC. An exploratory in-vivo study was performed in the pig with phosphatidylserine in two formulations; either in the form of PS/PC liposomes or together with Polysorbate 80 in the form of mixed micelles (phosphatidylserine/P80). Including phosphatidylserine in the formulations appeared to increase the availability, of subcutaneously administered r-VIII SQ in the pig. However, further studies are necessary, preferably in the monkey where in-vitro studies indicate a closer resemblance to the human. In conclusion, a proposed inactivation mechanism for r-VIII SQ in subcutaneous tissue could be adsorption to phospholipid surfaces followed by proteolytic degradation. However, additional studies are required due to the multitude of factors influencing the subcutaneous absorption route. A combination of protease inhibitor(s) together with phosphatidylserine-containing liposomes are suggested for further investigation, preferably in a monkey animal model.     

Multiple forms of long-term plasticity at unitary neocortical layer 5 synapses

Long-term potentiation and depression (LTP and LTD) are cellular plasticity phenomena expressed at a variety of central synapses, and are thought to contribute to learning and developmental changes in circuitry. Recurrent neocortical layer-5 synapses are thought to express a presynaptic form of LTP that influences the short-term plasticity of the synapse. Here we show that changes in synaptic strength elicited by pairing high frequency pre- and postsynaptic firing at this synapse result from a mixture of presynaptic and postsynaptic forms of plasticity, as assessed by the analysis of changes in coefficient of variation, short-term plasticity, and NMDA:AMPA current ratios. Pharmacological dissection of this plasticity revealed that block of presynaptic LTD with an endocannabinoid inhibitor enhanced LTP, while the apparently presynaptic component of LTP could be prevented by induction in the presence of blockers of nitric oxide. These data suggest that correlated high-frequency firing at layer-5 synapses simultaneously induces a mixture of presynaptic LTD, presynaptic LTP, and postsynaptic LTP.