Consenso chileno para la atención integral de niños y adultos con fibrosis quística / Chilean consensus for the integral care of children and adults with cystic fibrosis

Cystic Fibrosis (CF) is the most frequent hereditary disease in whites, with a reserved prognosis. Since 2003, Chile began a comprehensive National Cystic Fibrosis Program, directed by the Respiratory Health Unit of the Ministry of Health. To date, the main results of the Program record a significantly longer survival (average 27 years) and a significant reduction in the age of diagnosis of patients admitted from 2006 onwards. Access to Chilean Explicit Health Guarantees, the implementation of neonatal screening in some regions of the country, the organization and setting up of CF-trained teams of various specialties, has contributed to improving results. Although the main manifestations are of the respiratory and digestive system, the multisystemic nature of CF makes it necessary to know the different aspects involved in its management, in order to optimize the results of the treatment and the resources invested, both in the public and private sectors. This document is a review and an update on the main aspects of the diagnosis, monitoring and treatment of the respiratory and non-respiratory manifestations of CF.

La Fibrosis Quística (FQ) es la enfermedad hereditaria de pronóstico reservado más frecuente en raza blanca. Desde el año 2003, Chile inicia un Programa Nacional de Fibrosis Quística, de carácter integral, dirigido por la Unidad de Salud Respiratoria del Ministerio de Salud. Hasta la fecha, los principales resultados del Programa registran una significativa mayor sobrevida (promedio 27 años) y una significativa reducción en la edad de diagnóstico de los pacientes ingresados desde 2006 en adelante. El acceso a la canasta GES (Garantías Explícitas en Salud), la implementación del tamizaje neonatal en algunas regiones del país, la organización y la constitución de equipos entrenados en FQ de diversas especialidades, ha contribuido a mejorar los resultados. Si bien las principales manifestaciones son del aparato respiratorio y digestivo, el carácter multisistémico de la FQ obliga a conocer los distintos aspectos involucrados en su manejo, a fin de optimizar los resultados del tratamiento y los recursos invertidos, tanto en el sector público como privado. Este documento es una revisión y actualización sobre los principales aspectos del diagnóstico, seguimiento y tratamiento de las manifestaciones respiratorias y no respiratorias de la FQ.

[Changing patterns of medication prescription for COPD patients in France. Impact of long-acting muscarinic antagonists' availability]. / Évolution des traitements de fond entre 2001 et 2012 chez les patients atteints de BPCO en France. Impact de la mise à disposition des anticholinergiques de longue durée d'action.

INTRODUCTION: We studied the pattern changes over time of medication prescriptions for COPD and their conformity with French and international recommendations using data from patients in the prospective French cohort "Initiatives BPCO". METHOD: Eight hundred and forty-six patients have been included during a first period from August, 2001 till May 2006 (n=425) and a second period from June, 2006 till June, 2012 (n=421). The pivotal date was based on the tiotropium availability in France. RESULTS: During period 1, we recruited older patients (average 65 vs 64 years), less often women (19 vs 26 %) and having less severe airflow obstruction (mean FEV1 48 vs 54 %). The ICS prescriptions decreased in mild COPD, but there was no change for inhaled long-acting beta-2 agonist (LABA) (68 %). The use of LABA+LAMA association without ICS increased from 0.9 to 7 %, but remained lower than the fixed LABA+ICS association (26 %), less often prescribed than the triple association LABA+ICS+LAMA (32.5 % in period 2). The use of long-acting bronchodilators increased from 68 to 80 % between both periods. Vaccinations and rehabilitation remained insufficiently prescribed. LAMA had been added but did not appear to replace other drugs.

[Algorithms and urinary incontinence in the elderly. Assessment, treatment, recommendations and levels of evidence. Review]. / Algorithmes et incontinence urinaire des séniors : évaluations, traitements, recommandations et niveaux de preuve. Revue de la littérature.

OBJECTIVES: Search processing algorithms in a primary care setting, analyzing the specifics of care management for seniors suffering from urinary incontinence (UI), described the recommendations and levels of evidence of treatment. METHODS: A literature review carried out via PubMed® and websites of scientific societies with search keywords classified according to an algorithm. RESULTS: One hundred algorithms have been discovered in the field of evaluation and treatment of UI. Screening for UI risk factors began early on in the treatment of reversible or chronic comorbidities, avoiding iatrogenic. Specific clinical features (red flags) required specialized advice. Non-pharmacological conservative treatment should be offered first in line for seniors: behavioral therapy, changes in lifestyle, walk, treatment of constipation. For women, pelvic floor muscle training combined biofeedback and functional electrical stimulation. After failure and persistence of UI with urgency, the information of the risk of a possible urinary retention or cognitive impairments preceded the prescription of an anticholinergic and the measurement of post-voiding residue done by ultrasounds. Older age is not a cons-indication for surgery UI least invasive. The cough test and Bonney maneuver can confirm a masked stress urinary incontinence and/or an associated prolapse. Cases of failure of UI, doubtful diagnosis or programmed surgery required urodynamic assessment. CONCLUSION: Algorithms and recommendations of UI should remain a valuable aid to the clinical assessment, diagnosis and treatment of UI in the elderly.

Sex differences in serotonin-hypothalamic connections underpin a diminished sense of emotional well-being with increasing body weight.

BACKGROUND/OBJECTIVES: The neurobiological mechanisms linking obesity to emotional distress related to weight remain largely unknown. PARTICIPANTS/METHODS: Here we combined positron emission tomography, using the serotonin transporter (5-HTT) radiotracer [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, with functional connectivity magnetic resonance imaging, the Beck Depression Inventory (BDI-II) and the Impact of Weight on Quality of Life-Lite questionnaire (IWQOL-Lite) to investigate the role of central serotonin in the severity of depression (BDI-II), as well as in the loss of emotional well-being with body weight (IWQOL-Lite). RESULTS: In a group of lean to morbidly obese individuals (n=28), we found sex differences in the 5-HTT availability-related connectivity of the hypothalamus. Males (n=11) presented a strengthened connectivity to the lateral orbitofrontal cortex, whereas in females (n=17) we found strengethened projections to the ventral striatum. Both regions are known as reward regions involved in mediating the emotional response to food. Their resting-state activity correlated positively to the body mass index (BMI) and IWQOL-Lite scores, suggesting that each region in both sexes also underpins a diminished sense of emotional well-being with body weight. Contrarily to males, we found that in females also the BDI-II positively correlated with the BMI and by trend with the activity in ventral striatum, suggesting that in females an increased body weight may convey to other mood dimensions than those weight-related ones included in the IWQOL-Lite. CONCLUSIONS: This study suggests sex differences in serotonin-hypothalamic connections to brain regions of the reward circuitry underpinning a diminished sense of emotional well-being with an increasing body weight.

[Pediatric medulloblastoma: Retrospective series of 52 patients]. / Médulloblastomes de l'enfant: étude rétrospective portant sur 52 patients.

PURPOSE: Retrospective analysis of the results of 52 children irradiated for a medulloblastoma. PATIENTS AND METHODS: Between 1974 and 2012, 52 children with an average age of 6 years and a half (11 months-17 years and a half) were treated with surgery then with radiotherapy at the Comprehensive Cancer Centre of Strasbourg (France). For 44 children, the treatment consisted of a chemotherapy. RESULTS: After a mean follow-up of 106.6 months (7-446 months), 13 relapses and 24 deaths were observed. Overall survival at 5 years and 10 years were 62% and 57%, respectively. Disease-free survival at 5 years and 10 years were 80% and 63%, respectively. Univariate analysis found the following adverse prognostic factors: the existence of a postoperative residue, the positivity of the cerebrospinal fluid, the metastatic status and medulloblastoma of high-risk. Positivity of the cerebrospinal fluid remains a negative factor in multivariate analysis. CONCLUSION: These results confirm the survival rate obtained by a conventional approach (surgery then irradiation). Insufficiency of results and rarity of medulloblastoma require the establishment of international protocols.

The central nervous norepinephrine network links a diminished sense of emotional well-being to an increased body weight.

OBJECTIVES: The neurobiological mechanisms linking obesity to emotional distress remain largely undiscovered. METHODS: In this pilot study, we combined positron emission tomography, using the norepinephrine transporter (NET) tracer [(11)C]-O-methylreboxetine, with functional connectivity magnetic resonance imaging, the Beck depression inventory (BDI), and the impact of weight on quality of life-Lite questionnaire (IWQOL-Lite), to investigate the role of norepinephrine in the severity of depression (BDI), as well as in the loss of emotional well-being with body weight (IWQOL-Lite). RESULTS: In a small group of lean-to-morbidly obese individuals (n=20), we show that an increased body mass index (BMI) is related to a lowered NET availability within the hypothalamus, known as the brain's homeostatic control site. The hypothalamus displayed a strengthened connectivity in relation to the individual hypothalamic NET availability to the anterior insula/frontal operculum, as well as the medial orbitofrontal cortex, assumed to host the primary and secondary gustatory cortex, respectively (n=19). The resting-state activity in these two regions was correlated positively to the BMI and IWQOL-Lite scores, but not to the BDI, suggesting that the higher the resting-state activity in these regions, and hence the higher the BMI, the stronger the negative impact of the body weight on the individual's emotional well-being was. CONCLUSIONS: This pilot study suggests that the loss in emotional well-being with weight is embedded within the central norepinephrine network.

[Adult medulloblastoma: Retrospective series of 21 patients]. / Médulloblastomes de l'adulte: étude rétrospective portant sur 21 patients.

PURPOSE: Retrospective analysis of the results of 21 adults treated for medulloblastoma. PATIENTS AND METHODS: Between 1978 and 2011, 21 adults with an average age of 31 years (18.3-50) were treated with surgery then with radiotherapy (n=20) at the Comprehensive Cancer Center of Strasbourg. For some (n=12), treatment consisted of chemotherapy. RESULTS: After a mean follow-up of 122 months (19-423), six relapses and seven deaths were observed. Overall survival at 5 years and 10 years was 89.4 ± 7.1% for both. Disease-free survival at 5 years and 10 years was 79.6 ± 9.2% and 85.7 ± 7.6% and 60.6 ± 17.7%, respectively. CONCLUSION: The rarity of medulloblastoma, especially in adults and these results confirm the necessity of international protocols.

Efectos de la transferencia eléctrica capacitiva en el tejido dérmico y adiposo / Capacitive electric transference effects in dermal and adipose tissues

ObjetivosLa transferencia eléctrica capacitiva (TEC) es una nueva modalidad, usada por los fisioterapeutas en ortopedia y estética, que causa un calentamiento profundo mediante una radiofrecuencia de 0,55MHz.ObjetivosEl propósito de este estudio es analizar los efectos de la TEC en los adipocitos de la dermis y la hipodermis, como así también los cambios en el tejido conjuntivo.Material y métodosSeis conejos de la especie Oryctolagus cuniculus, familia Leporidae, tipo albinos, fueron divididos en dos grupos. El primero (n=4) recibió 6min de TEC en un área de 38cm2. El procedimiento fue repetido 8 veces. El otro (n=2) recibió terapia con placebo. Al final de la metodología, los conejos fueron sacrificados y se retiraron 3 muestras de cada animal que fueron empleadas para contar las células adiposas y analizar los cambios del tejido conjuntivo.ResultadosLa diferencia entre el grupo control y el tratado en el conteo de células adiposas en la dermis fue significativa (p=0,0135) y muy significativa (p=0,0015) en la hipodermis. La disminución de peso postratamiento no fue significativa (p=0,3851). El análisis cualitativo arrojó en nueve de las muestras tratadas lesión con disminución de la densidad del tejido conjuntivo y en las 3 restantes, lesión con incremento de la densidad. En las muestras control hubo 3 lesiones leves. Sólo se encontró inflación aguda en 3 de las muestras control y en ninguna muestra, inflamación crónica.ConclusiónLa diferencia significativa en el número de adipocitos no llevó a una reducción significativa de peso. La disminución de la densidad del tejido conjuntivo podría ser responsable de la efectividad de la TEC en la fibrosis y la celulitis. El incremento de la densidad podría explicar el efecto «lifting» a temperaturas mayores(AU)

AimsCapacitive Electric Transference (CET) is a new therapeutic modality used by physical therapists in orthopedic and esthetics that causes deep warning using a radiofrequency of 0.55MHz.AimsThe purpose of this study is to analyze the effects of CET in dermis and hypodermis adipocytes and the changes in the conjunctive tissue.MethodSix Oryctolagus Cuniculus- albino rabbits from the Loporidae family were divided into 2 groups. The first group (n=4) received 6 minutes of CET in an area of 38cm2. The process was repeated 8 times. The other group (n=2) received sham therapy. At the end of the treatment, the rabbits were sacrificed and 3 skin samples were obtained from each animal, and were used for adipose cells count and conjunctive tissue analysis.ResultsThere was a significant difference between the treated and sham group in adipose cells count in the dermis (p=0.0135) and a very significant difference (p=0.0015) in hypodermic tissue. Post-treatment weight decrease was not significant (p=0.3851).ResultsThe qualitative analysis found conjunctive tissue lesions with density decrease in 9 of the treated samples and a density increase in 3 of them. Mild lesion was also found in 3 of the sham samples. Acute inflammation was only found in 3 of the sham group samples and the chronic inflammation type was not found in any of the samples.DiscussionThe significant difference in adipose cells count did not cause a significant weight lost. The density decrease of conjunctive tissue could be reason for the effectiveness of CET in fibrosis and cellulites treatment. The density increase could explain the “lifting effect” at higher temperatures(AU)

Inflammatory disease processes and interactions with nutrition.

Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain omega-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression (omega-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are required.

Atlas vertebra realignment and achievement of arterial pressure goal in hypertensive patients: a pilot study.

Anatomical abnormalities of the cervical spine at the level of the Atlas vertebra are associated with relative ischaemia of the brainstem circulation and increased blood pressure (BP). Manual correction of this mal-alignment has been associated with reduced arterial pressure. This pilot study tests the hypothesis that correcting mal-alignment of the Atlas vertebra reduces and maintains a lower BP. Using a double blind, placebo-controlled design at a single center, 50 drug naïve (n=26) or washed out (n=24) patients with Stage 1 hypertension were randomized to receive a National Upper Cervical Chiropractic (NUCCA) procedure or a sham procedure. Patients received no antihypertensive meds during the 8-week study duration. The primary end point was changed in systolic and diastolic BP comparing baseline and week 8, with a 90% power to detect an 8/5 mm Hg difference at week 8 over the placebo group. The study cohort had a mean age 52.7+/-9.6 years, consisted of 70% males. At week 8, there were differences in systolic BP (-17+/-9 mm Hg, NUCCA versus -3+/-11 mm Hg, placebo; P<0.0001) and diastolic BP (-10+/-11 mm Hg, NUCCA versus -2+/-7 mm Hg; P=0.002). Lateral displacement of Atlas vertebra (1.0, baseline versus 0.04 degrees week 8, NUCCA versus 0.6, baseline versus 0.5 degrees , placebo; P=0.002). Heart rate was not reduced in the NUCCA group (-0.3 beats per minute, NUCCA, versus 0.5 beats per minute, placebo). No adverse effects were recorded. We conclude that restoration of Atlas alignment is associated with marked and sustained reductions in BP similar to the use of two-drug combination therapy.

[Endocrinology]. / Endocrinologie.

There is now convincing evidence that the risks of hormone replacement therapy in post-menopausal women exceed its benefits. Similarly, it has now been shown that the current use of low-dose oral contraceptives significantly increases the risk for cardiac and arterial thrombotic events. With regard to hypothyroidism, it is now clearly established that the adjunction of T3 to T4 does not offer any benefits. Furthermore, a study has now demonstrated that patients with no symptoms of coronary heart disease can be started safely on the full replacement dose of T4 rather than titrating the dose over a prolong period of time. Finally, several theses are now well documented where chinese herbal products contain thyroid hormones or glucocorticoids potentially leading to serious side effects and our patients should be informed about these dangers.

[Focus on dehydroepiandrosterone (DHEA)]. / Mise au point sur la déhydroépiandrostérone (DHEA).

Secreted by the adrenal cortex, DHEA exerts its action either indirectly in peripheral tissues after its conversion to androgens and estrogens, or directly as a neurosteroid through the interaction with neuronal receptors. Analyses of randomized studies show that treatment with DHEA improves well-being and fatigue in patients with adrenal insufficiency and reduces disease activity in women with systemic lupus erythematosus. Interesting results have also been observed in the treatment of depressive disorders, but these studies require confirmation. In contrast, there is neither justification for DHEA supplementation in healthy elderly subjects nor clear evidence for beneficial effects of DHEA on muscle function, bone metabolism or cognition. Finally, there is no guarantee with regard to the quality of the product or its safety during long term use.

[Primary intraocular lymphoma with unusual clinical presentation and poor outcome]. / Primäres intraokuläres Lymphom mit untypischer Klinik und ungünstigem Verlauf.

BACKGROUND: Primary intraocular lymphoma is a distinct subset of primary non-Hodgkin's lymphoma of the CNS. In general, the primary non-Hodgkin's lymphoma of the CNS is rare, accounting for 1 % of all non-Hodgkin's lymphomas and less than 1 % of all intraocular tumors. HISTORY AND SIGNS: A 70-year-old man was hospitalized in June 2002 because of acute loss of vision on his left eye. A severe vitreous hemorrhage was observed. Ultrasound showed solid subretinal lesions at the posterior fundus. Diagnostic vitreous surgery including a biopsy was performed. An intraocular malignant B-cell lymphoma was determined by immunohistochemistry. General screening revealed no further manifestations of the lymphoma. THERAPY AND OUTCOME: The patient initially refused any therapy until a painful secondary neovascular glaucoma with complete loss of visual function developed, thus prompting us to perform an enucleation. The following immunohistochemical examination confirmed the initial diagnosis. A chemotherapy with high-dose methotrexate and leucovorin rescue was initiated. CONCLUSIONS: Primary intraocular lymphoma can present as diffuse uveitis refractory to corticosteroids. Diagnosis can be difficult and is often delayed.

Localisation of motor areas in brain tumour patients: a comparison of preoperative [18F]FDG-PET and intraoperative cortical electrostimulation.

Assessment of the exact spatial relation between tumour and adjacent functionally relevant brain areas is a primary tool in the presurgical planning in brain tumour patients. The purpose of this study was to compare a preoperative fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET) activation protocol in patients with tumours near the central area with the results of intraoperative direct cortical electrostimulation, and to determine whether non-invasive preoperative PET imaging can provide results equivalent to those achieved with the invasive neurosurgical "gold standard". In this prospective study, we examined 20 patients with various tumours of the central area, performing two PET scans (each 30 min after i.v. injection of 134-341 MBq [18F]FDG) in each patient: (1) a resting baseline scan and (2) an activation scan using a standardised motor task (finger tapping, foot stretching). Following PET/MRI realignment and normalisation to the whole brain counts, parametric images of the activation versus the rest study were calculated and pixels above categorical threshold values were projected to the individual MRI for bimodal assessment of morphology and function (PET/MRI overlay). Intraoperative direct cortical electrostimulation was performed using a Viking IV probe (5 pulses, each of 100 micros) and documented using a dedicated neuro navigation system. Results were compared with the preoperative PET findings. PET revealed significant activation of the contralateral primary motor cortex in 95% (19/20) of the brain tumour patients (hand activation 13/13, foot activation 6/7), showing a mean increase in normalised [18F]FDG uptake of 20.5% +/- 5.2% (hand activation task) and 17.2% +/- 2.5% (foot activation task). Additionally detected activation of the ipsilateral primary motor cortex was interpreted as a metabolic indication for interhemispheric compensational processes. Evaluation of the PET findings by cortical stimulation yielded a 94% sensitivity and a 95% specificity for identification of motor-associated brain areas. In conclusion, the findings indicate that a relatively simple and clinically available [18F]FDG PET activation protocol enables a sufficiently precise assessment of the local relation between the intracranial tumour and the adjacent motor cortex areas and may facilitate the presurgical planning of tumour resection.

[Acute hemolysis following perioperative blood salvage in chldren operated for the surgical correction of craniosynostosis]. / Hémolyse aiguë au décours d'une chirurgie de correction d'une craniosténose utilisant l'autotransfusion périopératoire chez un nourrisson.

We report the case of a 6-month-old child, who suffered from acute haemolysis following transfusion of salvaged blood. This complication, of favourable outcome, was related to the accidental aspiration of benzalkonium chloride into the cell saver. This case emphasizes that any adjunction of antiseptic solution is contraindicated during blood saving. The use of a cell saver must be associated with written protocols, describing clearly the contraindications, precautions of use, and the different steps of use of this method of autologous blood transfusion.

Differential removal of thymidine nucleotide analogues from blocked DNA chains by human immunodeficiency virus reverse transcriptase in the presence of physiological concentrations of 2'-deoxynucleoside triphosphates.

Removal of 2',3'-didehydro-3'-deoxythymidine-5'-monophosphate (d4TMP) from a blocked DNA chain can occur through transfer of the chain-terminating residue to a nucleotide acceptor by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). ATP-dependent removal of either d4TMP or 3'-azido-3'-deoxythymidine-5'-monophosphate (AZTMP) is increased in AZT resistant HIV-1 RT (containing D67N/K70R/T215F/K219Q mutations). Removal of d4TMP is strongly inhibited by the next complementary deoxynucleoside triphosphate (50% inhibitory concentration [IC(50)] of approximately 0.5 microM), whereas removal of AZTMP is much less sensitive to this inhibition (IC(50) of >100 microM). This could explain the lack of cross-resistance by AZT-resistant HIV-1 to d4T in phenotypic drug susceptibility assays.

Perioperative blood salvage during surgical correction of craniosynostosis in infants.

Surgical correction of craniosynostosis in infants is a very haemorrhagic procedure. The aim of this study was to determine whether the perioperative use of the continuous autotransfusion system (CATS) would reduce homologous transfusion during repair of craniosynostosis. Two groups of patients were studied according to the availability of the CATS in our hospital. The control group had surgery before the system was introduced and the study group had operations subsequently. Use of CATS was associated with a significant decrease in the median (95% confidence interval) volume of homologous blood transfused [413 (250-540) ml in the control group versus 317 (150-410) ml in the CATS group, P = 0.02] and in the median (95% confidence interval) number of packed red cell units transfused [2 (1-2) in the control group versus 1 (1-2) in the CATS group, P = 0.04] in the perioperative period. Use of CATS is associated with a reduction in homologous transfusion during the surgical correction of craniosynostosis in infants.

123I-antileukoproteinase scintigraphy reveals microscopic cartilage alterations in the contralateral knee joint of rats with "monarticular" antigen-induced arthritis.

OBJECTIVE: To assess the involvement of the contralateral knee joint in monarticular antigen-induced arthritis (AIA) by scintigraphy with the cationic (pI >10), 123I-labeled, serine proteinase inhibitor antileukoproteinase (123I-ALP) and to compare the scintigraphic findings with those of radiography and high-resolution ex vivo magnetic resonance imaging (MRI). METHODS: Lewis rats with chronic AIA were examined 2.5 months following arthritis induction (injection of 500 microg of methylated bovine serum albumin/saline into the ipsilateral [arthritic] knee joint and injection of phosphate buffered saline into the contralateral knee joint following systemic immunization). 123I-ALP was injected intravenously into normal rats (n = 4) or rats with AIA (n = 6). The ipsilateral and contralateral knee joints and both ankles were examined by scintigraphy and radiography. Joint cartilage was examined by high-resolution ex vivo MRI, histopathology, and measurement of tissue radioactivity. RESULTS: ALP accumulation (typically observed in normal articular cartilage) was lost in both the ipsilateral and the contralateral knee joints, but not in the clinically unaffected ankles of rats with AIA. In both knee joints, 123I-ALP target:background ratios and cartilage radioactivity correlated negatively with the loss of toluidine blue staining in cartilage, which documents the depletion of charged matrix molecules. Findings of histopathology confirmed mild alterations in the ipsilateral knee joint and even milder alterations in the contralateral knee joint, while the ankles were normal. Radiography and high-resolution ex vivo MRI failed to detect abnormalities in the contralateral knee joint. CONCLUSION: Loss of ALP accumulation appears to document proteoglycan depletion, even in the microscopically altered cartilage of the contralateral knee joint in AIA. These findings underscore the high sensitivity of 123I-ALP for in vivo detection of biochemical cartilage alterations in arthritis, and furthermore, question the use of the contralateral knee joint as a normal control in AIA.

Tongue lip and jaw differentiation and its relationship to orofacial myofunctional treatment.

A number of developmental changes occur in eating patterns from infancy through childhood. Initially a primitive reflexive process, deglutition develops into a complex, integrated voluntary/reflexive process. The movements of the tongue, lips and mandible are easily observed to undergo a transformation from synergistic, undifferentiated movements in the infant, to differentiated and refined movements required for biting, chewing, bolus formation and propulsion in the toddler and young child. This transformation is also crucial for the development of higher levels of articulatory precision and coordination required for verbal communication. This developmental process does not always occur in individuals exhibiting orofacial myofunctional disorders. This article will review current research in this area as well as describe how to evaluate for normal tongue, lip and jaw differentiation, and present exercises to develop these skills, which are necessary for successful outcomes in orofacial myofunctional treatment.

Kinetic modeling of N-[11C]methylpiperidin-4-yl propionate: alternatives for analysis of an irreversible positron emission tomography trace for measurement of acetylcholinesterase activity in human brain.

N-[11C]Methylpiperidin-4-yl propionate ([11C]PMP) is a substrate for hydrolysis by acetylcholinesterase (AChE). This work evaluates kinetic analysis alternatives for estimation of relative AChE activity using dynamic positron emission tomography (PET) studies of [11C]PMP. The PET studies were performed on three groups of subjects: (1) 12 normal volunteer subjects, aged 20 to 45 years, who received a single intravenous injection of 16 to 32 mCi of [11C]PMP; (2) six subjects, aged 21 to 44 years, who received two 16-mCi injections of [11C]PMP (baseline and visual stimulation, respectively); and (3) five subjects, aged 24 to 40 years, who received two 16-mCi injections separated by 200 minutes (baseline and after a 1-hour constant infusion of 1.5 mg of physostigmine, respectively). Dynamic acquisition consisted of a 17-frame sequence over 80 minutes. All analysis methods were based on a first-order kinetic model consisting of two tissue compartments with the parameter k3, representing PMP hydrolysis, being the index of AChE activity. Four different schemes were used to estimate k3: (1) an unconstrained non-linear least-squares fit estimating blood-brain barrier transport parameters, K1 and k2, in addition to the hydrolysis rate constant k3; (2) and (3), two methods of constraining the fit by fixing the volume of distribution of free tracer (DVfree); and (4), a direct estimation of k3 without use of an arterial input function based on the shape of the tissue time-activity curve alone. Results showed that k3 values from the unconstrained fitting and no input methods were estimated with similar accuracy, whereas the two methods using DVfree constraints yielded similar results. The authors conclude that the optimal analysis method for [11C]PMP differs as a function of AChE activity. All four methods gave precise measures of k3 in regions with low AChE activity (approximately 10% coefficient of variation in cortex), but surprisingly, with unconstrained methods yielding estimates with lower variability than constrained methods. In regions with moderate to high AChE activity, constrained methods were required to yield meaningful estimates and were superior to the unconstrained methods.