Gait parameters in a reference sample of healthy Spanish schoolchildren: multivariate descriptive statistics and asymmetries observed in left and right cycles.

INTRODUCTION: Instrumental gait analysis is an emerging technology used increasingly to evaluate motor disorders in children. Normal reference data is necessary in order to evaluate patients, but there are few reference resources for the Spanish paediatric population. OBJECTIVE: We aim to describe the values of 16 clinically relevant gait variables in healthy Spanish schoolchildren, and identify any linear associations or left-right asymmetries. SUBJECTS AND METHODS: The values of 16 gait variables were determined in schoolchildren (n=27, aged 5-13 years) using instrumental gait analysis. We analysed asymmetries for each variable (Student's t-test for dependent samples) and calculated their confidence intervals (95% of the standardised difference in right and left means [SMD]). Values and associations between variables were represented using a heat map. RESULTS: Our project presents normal values tables for 16 variables in the gait cycle. Significant asymmetries were detected in the mean values for minimum hip flexion (SMD: 0.25 95% CI, 0.11-0.39) and peak hip abduction in swing (SMD: -1.05 95% CI: -1.71--0.27). Functional associations among gait variables are present. CONCLUSIONS: We present a reference dataset for Spanish school-aged children in which left-right asymmetries and functional associations may be observed for different variables.

The nigrostriatal system in the presymptomatic and symptomatic stages in the MPTP monkey model: a PET, histological and biochemical study.

Parkinson's disease (PD) is diagnosed when striatal dopamine (DA) loss exceeds a certain threshold and the cardinal motor features become apparent. The presymptomatic compensatory mechanisms underlying the lack of motor manifestations despite progressive striatal depletion are not well understood. Most animal models of PD involve the induction of a severe dopaminergic deficit in an acute manner, which departs from the typical, chronic evolution of PD in humans. We have used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered to monkeys via a slow intoxication protocol to produce a more gradual development of nigral lesion. Twelve control and 38 MPTP-intoxicated monkeys were divided into four groups. The latter included monkeys who were always asymptomatic, monkeys who recovered after showing mild parkinsonian signs, and monkeys with stable, moderate and severe parkinsonism. We found a close correlation between cell loss in the substantia nigra pars compacta (SNc) and striatal dopaminergic depletion and the four motor states. There was an overall negative correlation between the degree of parkinsonism (Kurlan scale) and in vivo PET ((18)F-DOPA K(i) and (11)C-DTBZ binding potential), as well as with TH-immunoreactive cell counts in SNc, striatal dopaminergic markers (TH, DAT and VMAT2) and striatal DA concentration. This intoxication protocol permits to establish a critical threshold of SNc cell loss and dopaminergic innervation distinguishing between the asymptomatic and symptomatic parkinsonian stages. Compensatory changes in nigrostriatal dopaminergic activity occurred in the recovered and parkinsonian monkeys when DA depletion was at least 88% of control, and accordingly may be considered too late to explain compensatory mechanisms in the early asymptomatic period. Our findings suggest the need for further exploration of the role of non-striatal mechanisms in PD prior to the development of motor features.

Evolutional patterns of articular cartilage following growth plate injury in rats.

BACKGROUND: No study to date has analyzed the damage of the articular cartilage and its relation to growth plate injury. The purpose of this study was to test whether primary injury to the growth plate contributes to secondary damage to the articular cartilage in rats. METHODS: A total of 109 two-week-old male Wistar rats were allocated to four lesional groups. In group I (controls) no surgery took place. In the remaining animals, an injury was caused in the proximal physis of the left tibia: group II, perichondrial ring injury; group III, direct injury to the growth plate; group IV, traumatic separation of the epiphysis where a Salter-Harris II-type injury was created. The results were assessed at 1 week, 6 weeks, and 6 months. A growth plate score was used. The stereological and histological changes in the articular cartilage were analyzed, and the results were subjected to statistical analysis. RESULTS: Histological studies showed discrete degenerative changes in the articular cartilage in the injured growth plate. Changes in the cell density, mean cell volume, and articular cartilage occurred in the injured growth plate. The changes appeared to be transient in groups II and III. CONCLUSIONS: Primary injury to the growth plate contributes to secondary damage to the articular cartilage in young rats. Our data -- extrapolated to the clinical view -- suggests that a Salter-Harris type II injury does not seem to have impunity to subsequent joint degeneration.

TP53 mutational pattern in Spanish and Polish non-small cell lung cancer patients: null mutations are associated with poor prognosis.

Inactivation of TP53 tumor suppressor gene is the most frequent molecular alteration in NSCLC, involving up to 60% of cases. Furthermore, TP53 mutational spectrum is related to the type of mutagen exposure, as well as racial and/or diet differences. Nearly 95% of TP53 perturbations affect codons included within exons 5-8 which encode for almost the entire DNA-binding domain. In this study we addressed the possible prognostic value of the molecular alterations identified in exons 5-8 of the TP53 gene in DNAs from 151 paraffin-embedded NSCLC sections corresponding to 59 Spanish and 92 Polish stage I-IIIA resected patients. PCR/single-strand conformation polymorphism (SSCP) analysis revealed that the occurrence of TP53 exon 5-8 mutations was 17/59 (29%) in the Spanish cohort and 17/92 (18%) in the Polish group. However, when DNA sequencing analysis was performed, these frequencies were reduced because of the presence of SSCP-false positive, intronic and silent mutations and polymorphisms. Fifteen of the 59 Spanish NSCLC tumors (25%) harbored TP53 mutations affecting exons 5-8 coding sequences, whereas only 12 of 92 Polish neoplasms (13%) contained alterations in the central hydrophobic region of p53. Our results indicate that the occurrence of TP53 mutations affecting exon 5-8 coding sequences in some European NSCLC populations may be lower than previously reported, and that the TP53 mutational patterns of these cohorts differ somewhat. The Spanish NSCLC patients contained missense mutations (9/59, 15%) and a relatively high percentage of null mutations (5/59, 8%) while the Polish patients mostly harbored missense mutations (9/92, 10%) and only one tumor contained a null type (1/92, 1%). Moreover, most TP53 missense mutations in the Spanish group were located outside the conserved regions, whereas the same mutations in the Polish group affected conserved amino acids. Furthermore, the Polish patients harbored a high percentage of G-->A transitions (most of them at non-CpG sites), while G-->T transversions were predominant in the Spanish group. Our findings suggest that there may be different racial or exogenous factors in these two populations which may help to explain both the distinct TP53 mutational pattern and the lower frequency obtained in the Polish group. The presence of missense mutations did not confer a worse clinical outcome in these subsets of NSCLC patients. However, patients whose tumors contained null TP53 gene mutations had a 5 month median disease-free survival time in contrast with 42 months in those patients without mutations (P=0.008). These findings suggest that loss of p53 function may enhance tumor progression in NSCLC patients independently of whether dominant negative TP53 missense mutations are present.

High levels of plasma FVIII and vWF in the toxic epidemic syndrome patients.

Factor VIII and von Willebrand factor proteins were evaluated in 115 patients having the chronic phase of the Toxic Epidemic Syndrome (TES), a new multisystemic disease probably caused by the ingestion of denatured rapeseed oil, and in 50 control volunteers. Higher circulating levels of factor VIII procoagulant activity (VIII:C) (158 +/- 58.4 U/dl), von Willebrand factor antigen (vWF:Ag) (166.1 +/- 55.5 U/dl) and von Willebrand factor ristocetin cofactor activity (vWF:RCo) (178.7 +/- 55.2 U/dl) were seen in TES patients (p less than 0.001, TES patients versus control subjects, for each parameter). The increased levels of vWF:Ag and vWF:RCo observed in TES patients correlated with the scleroderma like lesion of the skin, with the sicca syndrome and with Raynaud's phenomenon (p less than 0.01), but not with other clinical manifestations. The multimeric analysis of vWF in 92% of the TES patients was similar to that found in normal plasma, but in the remaining 8% a very slight increase of larger vWF multimers in plasma were observed. The raised levels of vWF found in TES patients in the chronic phase may reflect an "in vivo" vascular injury.

Cutaneous malignant melanoma and sun exposure in Spain.

Cutaneous malignant melanoma has an increasing importance all over the world. However very few epidemiological studies have been published from Spain, and Spanish people have not become aware of the problem. This study was designed to examine sun exposure patterns and other related items among 116 consecutive patients with melanoma and 235 controls. Each subject answered a questionnaire covering the place of residence, sun exposure details and other risk factors, and underwent a skin examination. Continuous sun exposure due to residence or occupation was associated with an odds ratio (OR) of 2.0 (95% confidence interval [CI] = 1.2-3.3). People who lived in the city but spent 50% of their time in rural areas for holidays had an OR of 2.2 (95% CI = 1.3-3.8) when compared with those living in urban and rural areas. The OR for people who sunbathed more than 30 times a year was 1.8 (95% CI = 1.2-2.8), and outdoor leisure time was also associated with melanoma appearance when exposure was greater than 60 units in the last 2 years, with an OR of 3.0 (95% CI = 1.6-5.5); 1 unit is equivalent to total body sun exposure for at least 2 h. These OR estimates were adjusted for age, skin type and the number of naevi. Construction workers (OR = 1.6; 95% CI = 0.5-5.6) had increased risk after adjustment for skin type, age and freckle count (OR = 4.3; 95% CI = 1.8 9.9) or mole count (OR = 2.8; 95% CI = 1.4-5.8). Working as a farmer was a protective factor after adjustment (OR = 0.5; 95% CI = 0.3-0.8). The use of sunscreens was a protective factor against melanoma (OR = 2.6; 95% CI = 1.6-3.6 for non-users). Campaigns should focus on advising people to avoid sun exposure in sunny places and to use sunscreens every time they are exposed to the sun.

ADA1/ADAp ratio in pleural tuberculosis: an excellent diagnostic parameter in pleural fluid.

We analysed the efficacy of pleural adenosine deaminase (ADAp) and the ADA1/ADAp ratio in the diagnosis of pleural tuberculosis in 103 pleural effusions, 27 of which were tuberculosis (TB) and 76 other diagnoses (non-TB). Smears, cultures and pleural biopsies were carried out in all cases, and were used for final diagnosis. The diagnostic yield of the parameters under study were as follows: smears/cultures of mycobacteria in fluid 11.1%/33.3%; biopsy 33.3%/51.8% and tuberculosis granulomas 85.1%. The levels of ADAp and ADA1/ADAp ratio in TB and non-TB groups showed very significant differences (P < 0.00001); in the TB group: ADAp 54.7 +/- 23.5 IU and ADA1/ADAp 0.27 +/- 0.08; in the non-TB group: ADAp 18.3 +/- 43.2 IU and ADA1/ADAp 0.64 +/- 0.14. The assay established ADA levels in pleural fluid > or = 40 IU and an ADA1/ADAp ratio < or = 0.42 as cut-off levels to identify individuals in the TB group, with a sensitivity of 88.8%/100%, a specificity of 92%/98.6%, a positive predictive value (PPV) of 80%/96.4%, a negative predictive value (NPV) of 95.8%/100% and an accuracy of 91.2%/99.02%. The ADAp levels in 27 patients with TB, showed close correlation with the number of monocyte macrophages (P = 0.001), but not with the number of lymphocytes (P = n.s.). The ADA1/ADAp ratio overcomes the limitations of ADAp (false positives and negatives), and is the most useful parameter for diagnosis on account of a high diagnostic yield, low cost and speed of the assay for identifying a pleural tuberculosis diagnosis, when compared with traditional methods.

Clinical and functional differences among patients with idiopathic anaphylaxis.

BACKGROUND: There are no studies assesing whether patients with idiopathic anaphylaxis are a heterogenous population OBJECTIVE: A study has been carried out to assess whether clinical and functional differences (mast cell releasability) exist between two sub-types of Idiopathic Anaphylaxis (Generalized Idiopathic Anaphylaxis -IA-G- and Idiopathic Anaphylaxis with Angioedema -IA-A-). METHODS: Patients were selected from the Idiopathic Anaphylaxis (IA) patient population of Hospital General de Albacete (Albacete, Spain) and this data were collected between 1990 and 1995. This series is composed of 81 patients. In the interest of seeing whether an IA classification is warranted between IA-G and IA-A, a logistic regression model was constructed in order to know if differences exist between IA-G and IA-A. To evaluate mast cell releaseability in different groups (IA-G, IA-A, atopic patients, urticaria and healthy subjects) we analysed the log 10 wheal area produced by four consecutive concentrations of codeine (from 90 to 3,3 mg/ ml). In those patients with IA-G, the variable urticaria was controlled, but not in those with IA-A. A parallel line assay was used to study the differences arising among all groups. When the conditions of parallelism and linearity were not fulfilled, a Hotelling's T2 test was performed. RESULTS: In the logistic regression equation total IgE, with an O.R. of 1.006 (95% C.I. 1.001-1.01) favoured the presence of IA-G; whereas the presence of urticaria did not favour the presence of IA-G, with an O.R. of 0.159 (95% C.I. 0.04-0.507). IA-G and IA-A patients showed a higher cutaneous reaction to codeine than atopic patients (p=0.005 and p=0.001 respectively). However, IA-G patients had a lower reaction to codeine than those patients with urticaria (p=0.048). No differences were observed among patients with IA-A and patients with urticaria, as was the case between IA-A and IA-G patients with respect to cutaneous response to codeine. CONCLUSION: Apparently, IA-G patients appear to be closely related to the presence of atopy, while IA-A patients are closely related to the presence of urticaria. Along with other unknown factors, an enhanced mast cell releaseability may explain these episodes of Idiopathic Anaphylaxis among atopic patients.

A comparative MRI study for white matter hyperintensities detection: 2D-FLAIR, FSE PD 2D, 3D-FLAIR and FLAIR MIP.

OBJECTIVE: The main objective of this study was to not only determine the most appropriate sequence for the analysis of white matter hyperintensities (WMH) on MRI but also to confirm the advantage of three-dimensional (3D) acquisition, as it has been suggested in previous studies, and to test the convenience of using maximum intensity projection (MIP) algorithms on 3D-fluid-attenuated inversion-recovery (FLAIR) images for a quicker evaluation of brain MR studies. METHODS: The number of WMH was compared in 40 patients and a control group of 10 volunteers using 4 different imaging modalities: two dimensional (2D)-FLAIR, 2D fast spin echo proton density (FSE PD), 3D-FLAIR and FLAIR MIP. Four experienced radiologists took part in the imaging analysis. All studies were performed on a 1.5-T whole-body MR unit. RESULTS: A statistically significant difference between the number of lesions detected on 3D acquisitions (FLAIR CUBE® or FLAIR MIP sequences) compared with those on 2D-FLAIR or 2D FSE PD was demonstrated. There is no significant difference between 3D-FLAIR and FLAIR MIP, therefore both of them can be used with similar results. CONCLUSION: 3D-FLAIR sequences should replace conventional 2D-FLAIR and/or FSE PD sequences in the MR acquisition protocol when WMH are suspected. MIP reformat algorithms are less time consuming, therefore these can also be used to simplify the detection. ADVANCES IN KNOWLEDGE: 3D sequences are superior for WMH depiction. Moreover, MIP algorithms allow easier analyses with similar results.

Severe hypoxaemia with a left ventricular assist device in a minipig model with an undiagnosed congenital cardiac disease.

We describe the placement of a left ventricular assist device (LVAD) in a pig with spontaneously occurring atrial septal defect (ASD) (incidental finding) that created a right-left cardiac shunt, with subsequent severe hypoxaemia. Early diagnosis was critical in order to prevent end-organ damage due to hypoxaemia. Adequate monitoring alerted us to the deterioration in oxygenation, haemodynamics and cerebral oxygen metabolism. This forced us to change the level of assistance provided by the pump, and thus dramatically correct this impairment. Necropsy revealed an ostium secundum ASD. In conclusion, if hypoxaemia presents after implementation of an LVAD, the presence of a right-left shunt must be ruled out. The first step must be a judicious reduction in assist device flow to minimize intracardiac shunting. Subsequently, atrial septal closure of the defect should be considered. We report an experimental model of severe hypoxaemia after placement of an LVAD as part of a larger research project.

[Monocyte chemotaxis: critical evaluation of 2 methods of quantification]. / Quimiotaxis de monocitos: valoración crítica de dos métodos de cuantificación.

The mononuclear phagocytic system (Mo) possesses a series of well defined functions regarding both its circulatory components--monocytes--and histiocytic macrophages. These functions--antimicrobial defense, elimination of cellular particles or detritus, immunological interaction with lymphocytes cells, antitumoral defense and control of granulopoiesis--require chemotaxis and phagocytosis or preceding steps. Although knowledge of these functional aspects is continually becoming better--always assured by advances obtained in the study of the function and pathology of polymorphonuclear cells--, an authentic pathology of monocyte chemotaxis as an independent clinical entity doesn't exist. This is attributed to of these cells. The techniques currently in use differ not only in their methodology but also in their bases and thus the results obtained by various authors are not generally comparable. All this led us to do a comparative study, in control subjects, between two techniques which explore the chemotactic capacity of monocytes from peripheral blood. The chemotactic capacity of monocytes from peripheral blood in control subjects, measured by two distinct quantification methods, were studied: Radioanalytic Method (monocytes tagged with 99 mTc) and a morphological method (counting the number of monocytes per field in immersion). The results obtained from both techniques were very similar, the existence of significant differences in cell behavior with exposure to the different chemotactic substances used could not be demonstrated. These results are commented on.