Box and block test, hand grip strength and nine-hole peg test: correlations between three upper limb objective measures in multiple sclerosis.

BACKGROUND AND PURPOSE: Limited data are available in the literature for upper limb impairment in multiple sclerosis (MS). This study aimed to report the distribution of values of hand grip strength (HGS), of the box and block test (BBT) and of the nine-hole peg test (9HPT) correlated with demographic and clinical data in subjects with MS. METHODS: This study involved five Italian neurological centres. The inclusion criteria were age ≥ 18, MS diagnosis, stable disease phase, right-hand dominance. All subjects underwent HGS, BBT and 9-HPT evaluation. RESULTS: In all, 202 subjects with MS were enrolled: 137 females; mean age 48.4 years; mean Expanded Disability Status Scale (EDSS) 4.17; mean disease duration 14.12 years; disease course 129 relapsing-remitting, 21 primary progressive and 52 secondary progressive MS subjects; mean right HGS 25.3 kg, left 23.2 kg; mean right BBT 45.7 blocks, left 44.9 blocks; mean right 9-HPT 30.7 s, left 33.4 s. All results were statistically significantly different compared to healthy controls. HGS, BBT and 9-HPT were associated with age, EDSS and disease duration, whilst disease course correlated with BBT and 9-HPT. The BBT and 9-HPT scores significantly differed according to level of disability (EDSS ≤3.0, 3.5-5.5, ≥6.0). CONCLUSION: Hand grip strength and BBT value distribution in a large MS population is reported. Correlations between HGS, BBT and 9-HPT were generally low.

Evaluation of the impact of buffered peptone water composition on the discrimination between Salmonella enterica and Escherichia coli by Raman spectroscopy.

The detection of Salmonella spp. in food samples is regulated by the ISO 6579:2002 standard, which requires that precise procedures are followed to ensure the reliability of the detection process. This standard requires buffered peptone water as a rich medium for the enrichment of bacteria. However, the effects of different brands of buffered peptone water on the identification of microorganisms by Raman spectroscopy are unknown. In this regard, our study evaluated the discrimination between two bacterial species, Salmonella enterica and Escherichia coli, inoculated and analyzed with six of the most commonly used buffered peptone water brands. The results showed that bacterial cells behaved differently according to the brand used in terms of biomass production and the spectral fingerprint. The identification accuracy of the analyzed strains was between 85% and 100% depending on the given brand. Several batches of two brands were studied to evaluate the classification rates between the analyzed bacterial species. The chemical analysis performed on these brands showed that the nutrient content was slightly different and probably explained the observed effects. On the basis of these results, Raman spectroscopy operators are encouraged to select an adequate culture medium and continue its use throughout the identification process to guarantee optimal recognition of the microorganism of interest.

Anorectal atresia with gross terminal colonic distension in Africa.

UNLABELLED: Anorectal malformation (ARM) is a group of significant birth defects with geographic variation in incidence, individual phenotypes and regional geographic subtypes occurring in approximately 1:5,000 live births. Anorectal atresia with gross terminal colonic distension in the presence of an absent anal canal has also been known as 'pouch colon' which is mainly associated with the Indian subcontinent. Its prevalence is unknown but it is rare, possibly representing a fraction of 1 % of ARM. The problem seems to revolve around the gross terminal distension of the distal pouch which remains a significant surgical challenge to surgeons resulting in poorer postoperative continence in many instances. AIM: This study set out to collate data on ARM patients with gross terminal distension of the distal pouch from Africa to evaluate its epidemiology and outcome in African patients. METHODS: Fifteen African paediatric surgical centres (7 South African and 8 African centres) were polled on the occurrence of anorectal atresia with gross terminal distension of the terminal bowel, an ARM variant. Data included ethnic group, age, gender as well as the anatomical pathology, classification and presence or absence of associated anomalies. RESULTS: Of 12 respondents, 8 (67 %) responded and sufficient data to classify and analyse were obtained from six of the eight positive replies (7 new cases). Abdominal X-ray showed a grossly dilated terminal portion of the colon in the presence of an imperforate anus. A colovesical fistula was observed in four (three males and one female cloaca). Three were associated with a colonic atresia, of which two were in the transverse colon and one in the sigmoid colon. Surgical corrective procedures were carried out in six, but one patient, with a cloaca, died prior to surgical correction. CONCLUSIONS: In this survey of 15 African centres, we have attempted to document the occurrence and presentation of anorectal atresia with gross terminal distension in Africa and report seven additional new cases. A possible association with associated conditions like colonic atresia requires further investigation.

Retrospective surveillance of intussusception in South Africa, 1998-2003.

BACKGROUND: Intussusception is a common gastrointestinal emergency in children and appears to have a somewhat different clinical spectrum in developing countries. Its etiology is still unclear, but a link to infective agents and viruses has been highlighted. This study aimed to assess the clinical spectrum and prevalence of intussusception in children from the diverse South African population. METHODS: Retrospective data were obtained from 9 participating pediatric referral units on the occurrence of intussusception in South African children (<14 years old) during a 6-year period (1998-2003). Results were correlated with national population statistics. Intussusception was anatomically classified into ileoileal, ileocolic, and colocolic types. The clinical features, management, outcome, and possible causes were examined. RESULTS: We reviewed the occurrence and clinical spectrum of intussusception in 423 children (age, 0-14 years) presenting with acute intussusception to 9 pediatric surgical centers. The mean duration of symptoms was 1.5 days, but a delayed presentation was common (median delay, 2.3 days). Intussusception occurred throughout the year, with a peak in the summer months. The majority of patients (89%) were <2 years old, and 78% presented at age 3-18 months of age. Crude population estimates indicate an occurrence of 1 case per 3123 population <2 years old. Only 11% of patients presented after 2 years of age, and the age at presentation was significantly lower (P < .05) in black African patients. All ethnic groups were affected. In 84% of patients, intussusception occurred at the ileocolic region junction, in 7% it was ileoileal, and in 9% it was colocolic. Colocolic intussusception appeared more common in black African patients, and associated pathologic conditions (polyps and Burkitt's lymphoma) occurred mainly in older children. Surgical intervention was required in 81% of patients and involved resection of gangrenous bowel in 40%. CONCLUSION: Intussusception appears to be a relatively frequent occurrence in children in South Africa. Although the clinical spectrum appears to vary, there is an apparent link to intestinal infection, which requires further investigation. A collaborative approach is required to ascertain the relationship of intussusception to preventable infections and to improve its diagnosis and management.

A comparison of upper limb function in subjects with multiple sclerosis and healthy controls using an inertial measurement unit.

Upper limbs (UL) dysfunction is frequent in people with Multiple Sclerosis (PwMS). Several objective measures of UL function are proposed; however, their use is mostly confined to assess subjects with mild-to-moderate disability and requires fine motor skills, often impaired in high disability level subjects. Thus, a tool to score UL function in the advanced disease stage is lacking. The aim of the study is to analyse and compare UL unilateral and bilateral movements of healthy control (HC) and PwMS, at different disability levels, using an instrumented version (Inertial Measurement Unit, IMU) of the 15-seconds finger-to-nose test (FNT). Each movement cycle was segmented in going/adjusting/returning phases. The inter-hand interval (IHI) allowed assessing bilateral coordination (i.e. synchrony) in each phase. The larger IHI, the more severe the bilateral coordination impairment is. After stratifying PwMS for disability level (PwMSLOW, Expanded Disability Status Scale, EDSS≤5.5 and PwMSHIGH, EDSS≥6), the ANOVA on IHI showed significant differences between PwMS and HC (p<0.001) in all phases. However, only the going phase IHI showed significantly higher asynchrony in PwMSHIGH than PwMSLOW and HC (p<0.001) and no differences between PwMSLOW and HC. The going phase IHI seems to be a clinical marker specific for high disability level PwMS. These findings suggest inertial sensors during FNT could be an easy-to-use method for a more detailed quantitative characterization of UL function in PwMS also in subjects with EDSS greater than 6.

Nine Hole Peg Test asymmetry in refining upper limb assessment in multiple sclerosis.

BACKGROUND: The Expanded Disability Status Scale (EDSS) is the most frequently used scale to measure neurologic impairment and quantify the level of disability in Multiple Sclerosis (MS) even though the scale focuses on ambulation and undervalues upper limb (UL) impairment. The 9-Hole Peg Test (9-HPT) is the gold standard for UL assessment in MS, calculating a mean score from right and left arms, even though subjects with MS often show a lateralization of neurological deficit. OBJECTIVE: The study aimed to determine whether an interaction exists between mean right-left 9-HPT scores or 9HPT score asymmetry (difference between right and left side) in predicting EDSS in MS subjects. METHODS: Demographic and disease variables and 9-HPT scores were obtained from medical records of individuals with MS collected in an ad-hoc database. Subjects with 9-HPT score ≤180 s for each arm were included. An asymmetry score was represented as the absolute value of the difference between 9-HPT scores for both arms. RESULTS: 549 subjects were included: 67.8% female, mean age 45±13.14 years, mean EDSS 3.98±2.12, 356 relapsing-remitting, 68 primary and 125 secondary progressive, mean 9-HPT scores: right arm 30.20 ± 19.99 s, left arm 31.80 ± 20.35 s. Mean asymmetry was 9.35±18.20 s. Correlation between mean right-left 9-HPT scores and EDSS was 0.58 (p<.001). Significant interaction between mean right-left 9-HPT scores and 9-HPT asymmetry in predicting EDSS scores was found. Regression slope of EDSS on mean right-left 9-HPT score decreases as asymmetry value increases (non-significance area values ≥ 40.93 s). CONCLUSIONS: Findings suggest interaction exists between mean right-left 9-HPT scores and asymmetry in predicting EDSS. A consequence of this is that, by disregarding information about asymmetry, studies exploring the association between mean right-left 9-HPT scores and global measures of disability may provide biased results. The bias tends to increase as asymmetry increases, and to be most prevalent among patients with EDSS scores > 6.

[A prospective auto-controlled study to evaluate the interest of selected sperm morphology to inseminate oocytes during IVF]. / Evaluation d'une procédure d'insémination des ovocytes en FIV classique tenant compte de la morphologie des spermatozoïdes sélectionnés.

OBJECTIVES: Since we observed in our laboratory a significant decrease of the fertilization rate in the classical IVF procedure compared to ICSI, we wanted to evaluate a new insemination procedure, using sperm morphology of selected semen as a criterion taken into account to calculate the number of mobile sperm to inseminate. PATIENTS AND METHODS: Therefore, we designed a prospective autocontrolled study which took place from September 2006 to May 2007. All IVF attempts resulting from infertile couples were included in the study if a previous analysis (lesser than one year) of sperm parameters performed in our laboratory was assessed as normal. The retrieved oocytes were separated into two groups (sibling ovocytes), inseminated randomly either with the usual procedure (control group) or with the tested protocol (tested group). Fertilization rate was the primary end point to evaluate this assay. Polyspermy rates were also compared. Subsequently, embryonic quality and development were assessed to eliminate an oxidative stress impact. Paired Student t-test was applied for statistical analysis. RESULTS: In all, 130 couples were included. The diploid fertilization rate was significantly increased in the tested group compared to the control group (66.9% vs 61.3%; p=0.017). No statistically significant difference was showed between the polyspermy rate and numbers of (i) good quality embryos and (ii) blastomeres per embryo into the two groups. DISCUSSION AND CONCLUSION: Compared with the conventional insemination procedure, the fertilization rate benefited from the tested insemination method in our laboratory without damaging embryonic growth. In the limit of our procedure, selected sperm morphology should be used to inseminate an appropriate number of spermatozoa within oocytes, even in case of normal semen values.

Modelling the exposure to chemicals for risk assessment: a comprehensive library of multimedia and PBPK models for integration, prediction, uncertainty and sensitivity analysis - the MERLIN-Expo tool.

MERLIN-Expo is a library of models that was developed in the frame of the FP7 EU project 4FUN in order to provide an integrated assessment tool for state-of-the-art exposure assessment for environment, biota and humans, allowing the detection of scientific uncertainties at each step of the exposure process. This paper describes the main features of the MERLIN-Expo tool. The main challenges in exposure modelling that MERLIN-Expo has tackled are: (i) the integration of multimedia (MM) models simulating the fate of chemicals in environmental media, and of physiologically based pharmacokinetic (PBPK) models simulating the fate of chemicals in human body. MERLIN-Expo thus allows the determination of internal effective chemical concentrations; (ii) the incorporation of a set of functionalities for uncertainty/sensitivity analysis, from screening to variance-based approaches. The availability of such tools for uncertainty and sensitivity analysis aimed to facilitate the incorporation of such issues in future decision making; (iii) the integration of human and wildlife biota targets with common fate modelling in the environment. MERLIN-Expo is composed of a library of fate models dedicated to non biological receptor media (surface waters, soils, outdoor air), biological media of concern for humans (several cultivated crops, mammals, milk, fish), as well as wildlife biota (primary producers in rivers, invertebrates, fish) and humans. These models can be linked together to create flexible scenarios relevant for both human and wildlife biota exposure. Standardized documentation for each model and training material were prepared to support an accurate use of the tool by end-users. One of the objectives of the 4FUN project was also to increase the confidence in the applicability of the MERLIN-Expo tool through targeted realistic case studies. In particular, we aimed at demonstrating the feasibility of building complex realistic exposure scenarios and the accuracy of the modelling predictions through a comparison with actual measurements.

Progressive increases of protein synthesis in the circumventricular organs during chronic dehydration in rats.

The quantitative autoradiographic method with L-(35S)methionine was applied to investigate the effect of chronic dehydration on rates of protein synthesis in circumventricular organs (CVOs). Water deprivation for 1, 2 and 3 days causes progressive increases of protein synthesis in the subfornical organ (SFO), the area postrema, the organum vasculosum laminae terminalis and the neurohypophysis. Chronic salt ingestion with 2% NaCl in drinking water for 3 days resulted in increases of protein synthesis in the CVOs similar to those found after 3 days water deprivation, with only one exception, the SFO, in which the rise in protein synthesis was of lower amplitude after 3 days salt ingestion as compared to 3 days water deprivation. These results suggest that several circulating factors related to intracellular dehydration and the high plasma levels of the neurohormones vasopressin and oxytocin are probably important determinants of the rise of protein synthesis in circumventricular organs. Alternatively, the elevated level of blood-borne angiotensin II may well explain the higher metabolic response of the SFO following water deprivation compared to salt ingestion.

In vivo imaging of fatty acid incorporation into brain to examine signal transduction and neuroplasticity involving phospholipids.

An in vivo method is presented that allows quantification and imaging of fatty acid incorporation into different brain phospholipids in relation to membrane synthesis, neuroplasticity, and signal transduction. The method can be used with positron emission tomography, and may help to evaluate brain phospholipid metabolism in humans with brain tumors, neurodegenerative disease, cerebral ischemia or trauma, or neurotoxic effects of drugs or other agents.

Comparison of the effects of chronic water deprivation and hypertonic saline ingestion on cerebral protein synthesis in rats.

The effects of 3 days water deprivation and 3 days with 2% (w/v) NaCl in drinking water on local rates of methionine incorporation into brain proteins were compared by means of a quantitative autoradiographic method with L-[35S]methionine. The two conditions of chronic dehydration resulted in large increases in the rate of methionine incorporation in the supraoptic (SON), magnocellular paraventricular (mPVN) and arcuate nuclei of the hypothalamus, and in the subfornical organ (SFO). Significant increases of lower amplitude occurred as a result of both treatments in the anteroventral third ventricle area, parvocellular paraventricular nucleus and locus coeruleus. Water deprivation caused larger increases of protein synthesis than hypertonic saline ingestion in the SON, mPVN and SFO. These results indicate that following chronic dehydration, increases in protein synthesis occur mainly in forebrain areas involved in the regulation of water balance, whereas no major changes in protein synthesis occur in brainstem areas involved in the control of blood volume and pressure.

Cerebral protein synthesis alterations in response to acute and chronic immobilization stress in the rat.

The quantitative autoradiographic method with L-(35S)methionine was used to determine the effects of 1-acute (4h) and 2-chronic (14 days) immobilization stress followed by one week of recovery. Acute stress induced a significant decrease in methionine incorporation into proteins in 17 of the 35 brain structures examined (mean effect: -22%), and a significant increase in the prepositus hypoglossal nucleus (+23%). Chronic stress induced a significant decrease in methionine incorporation into proteins in 8 of the 35 structures analyzed. Only 4 structures were similarly affected in both these conditions. Our results indicate that stress-induced specific molecular changes in brain are also associated with changes in more general molecular components of cellular metabolism.

Inhibition of methionine incorporation into brain proteins after the systemic administration of p-chlorophenylalanine and L-5-hydroxytryptophan.

The effects of p-chlorophenylalanine (p-CPA) and L-5-hydroxytryptophan (L-5-HTP) on local rates of plasma methionine incorporation into brain proteins were investigated by a quantitative autoradiographic method. The sequential i.v. administration of p-CPA (280 mg/kg, 42 h before the measurement) and L-5-HTP (60 mg/kg, 40 min before the measurement) resulted in an average 82% decrease of plasma methionine incorporation. The two treatments given separately also reduced the rates of plasma methionine incorporation in all the brain areas examined by 33 and 50%, respectively for p-CPA and L-5-HTP. These results indicate that: (1) p-CPA and L-5-HTP, two drugs which affect brain serotonin production in opposite ways, both produce large and general decreases of brain protein synthesis; (2) the administration of L-5-HTP does not restore the p-CPA-induced inhibition of brain protein synthesis but induces further decreases of protein synthesis. These results suggest that the reduction of brain protein synthesis in p-CPA-treated rats is mainly related to high circulating levels of p-CPA and phenylalanine; and that brain serotonin is not the only factor involved in the widespread metabolic changes observed. Such profound alterations of brain metabolism should be considered when interpreting the behavioral and neurochemical effects of p-CPA and L-5-HTP.

Decreased protein synthesis in hypothalamic nuclei following L-5-hydroxytryptophan in intact and p-chlorophenylalanine-pretreated rats.

The rate of protein synthesis was estimated in individual hypothalamic nuclei by a quantitative autoradiographic technique with L-[35S]methionine. The i.v. administration of 60 mg/kg L-5-hydroxytryptophan (40 min before) resulted in a 45-55% decrease of overall protein synthesis rate in all the hypothalamic nuclei examined. In rats pretreated (42 h before) with a single i.v. injection of 280 mg/kg p-chlorophenylalanine, a drug which is known to deplete brain serotonin concentration, the administration of 60 mg/kg L-5-hydroxytryptophan resulted in a 50-75% decrease of protein synthesis rates in the hypothalamic nuclei. These results suggest that the systemic administration of large doses of L-5-hydroxytryptophan may inhibit protein synthesis in hypothalamic nuclei directly or indirectly after the conversion of this compound to serotonin.

Restraint stress and adrenalectomy do not affect the level of rat cerebral enolase.

Gamma gamma (gamma gamma) enolase amount and enolase isozyme activities were measured in brain structures involved in stress response (hypothalamic paraventricular and supraoptic nuclei, locus coeruleus, hippocampus, A1 and A2 regions, hypophysis). Analyses were made in rats after immobilization or adrenalectomy, two experimental conditions that have been reported to increase brain glucose consumption and protein synthesis. In control rats enolase content was highest in the A1 region and hippocampus and lowest in hypophysis. A positive correlation was found between the enzyme level and its activity in the brain regions studied. However, in stressed or adrenalectomized rats, the level of glycolytic enzyme enolase was not significantly modified.

Docosahexaenoic acid (cervonic acid) incorporation into different brain regions in the awake rat.

A quantitative method is presented to examine the localization, in individual brain regions of awake rats, of docosahexaenoic acid (22:6 n-3 or cervonic acid), the main polyunsaturated fatty acid of the nervous system together with arachidonic acid. Following the intravenous injection of 10 microCi [14C]22:6 n-3 (around 0.2 mumol/rat). 0.11-0.28% of the initial radioactivity was located in specific brain areas after detection from 10 to 240 min. Brain regional radioactivity determined by quantitative autoradiography indicated that 60 min after injection, [14C]22:6 n-3 concentrations ranged from 13.75 nCi/g of tissue in inferior olive to 5.59 nCi/g in frontal cortex. The results indicate a higher incorporation into the auditory system: inferior colliculus, central cochlear nucleus, lateral lemniscus, into neuroendocrine structures: paraventricular and supraoptic nuclei, and into certain circumventricular organs such as the pineal gland and neurohypophysis. Analysis of the Bligh and Dyer lipid extracts of rat brain revealed that 60 min after injection, 80-85% of the radioactivity was in choline and ethanolamine phosphoglycerides. These observations suggest that intravenous injection of [14C]22:6 n-3 may be used to study the brain lipid compartmental metabolism in vivo in order to visualize alterations of structural lipid components.

Lithium decreases turnover of arachidonate in several brain phospholipids.

In vivo rates of incorporation and turnover of palmitate and arachidonate in brain phospholipids were measured in awake rats treated chronically with lithium, following intravenous infusion of radiolabeled palmitate and arachidonate, respectively. Chronic lithium, at a brain level considered to be therapeutic in humans, decreased turnover of arachidonate within brain phosphatidylinositol, phosphatidylcholine and phosphatidylethanolamine by up to 80% (P < 0.001). In contrast, lithium had a minimal effect on turnover of palmitate, causing only a 26% reduction in turnover in phosphatidylcholine (P < 0.01). These results suggest that a major therapeutic effect of lithium is to reduce turnover specifically of arachidonate, possibly by inhibiting phospholipase A2 involved in signal transduction. The effect may be secondary to the known action of lithium on the phosphoinositide cycle, by inhibiting the activity of inositol monophosphatase.

Widespread increase in brain protein synthesis following acute immobilization stress in adult rat brain.

The autoradiographic method with [L-35S]methionine was used to determine the effects of a 2 h acute immobilization stress followed by a 4 h recovery on local rates of protein synthesis in the adult rat brain. Methionine incorporation into proteins was significantly increased (from 17 to 86%) in 37 out of the 39 analyzed brain structures. These results show that the stress-induced activation of the overall rate of brain protein synthesis may persist for at least 4 h after cessation of the stimulus even though the stress-related physiological variables have returned to basal levels. They suggest that increased protein synthesis may play a key role in the molecular events which lead to the neuronal plastic changes following an acute stress.

Problems of management of burns injuries among children.

BACKGROUND: Contrary to our local experience, published data elsewhere show increased survival rates from major burns due to improvements in management. This study aimed at examining problems of burns management in children. DESIGN: Relevant data extracted from the records of 44 children included sociodemographic, clinical, management characteristics and outcomes. RESULTS: There were 86.0% thermal burns due to accidental, domiciliary events in 36 (81.8%. Mean (range) BSA was 35.9% +/- 4.0 (1%-95%), mostly 2nd degree burns in 34 (77.3%). Mean (range) duration of symptoms before presentation was 1.1 +/- 0.3 days (1-7 days). Following hospitalisation, involvement of key experts in acute burns care was either delayed or omitted. Intensive care monitoring and support including mechanical ventilation were unavailable for 11 (25.0%) cases with cardiorespiratory compromise. Septicaemia & pneumonias were associated with death in 9 (56.3%) of the 16 deaths. Klebsiella, pseudomonas and coliform organisms were isolated from most burns wound. Oral acetominophen and intramuscular dipyrone were the main analgesics used in 24 (54.6%) and 8 (18.2%) cases respectively. Anxiolytics were used in only 2 94.5%). Case fatality rate was 36.4%. Mortalities were 100% with BSA 50-100% (p=0. 000). CONCLUSION: Prevention and improvements in management of burns including early multidisciplinary care, critical care support, aggressive wound care and adequate pain control should be emphasised.