Evolutionary Patterns of Modularity in the Linkage Systems of the Skull in Wrasses and Parrotfish.

The concept of modularity is fundamental to understanding the evolvability of morphological structures and is considered a central framework for the exploration of functionally and developmentally related subsets of anatomical traits. In this study, we explored evolutionary patterns of modularity and integration in the 4-bar linkage biomechanical system of the skull in the fish family Labridae (wrasses and parrotfish). We measured evolutionary modularity and rates of shape diversification of the skull partitions of three biomechanical 4-bar linkage systems using 205 species of wrasses (family: Labridae) and a three-dimensional geometric morphometrics data set of 200 coordinates. We found support for a two-module hypothesis on the family level that identifies the bones associated with the three linkages as being a module independent from a module formed by the remainder of the skull (neurocranium, nasals, premaxilla, and pharyngeal jaws). We tested the patterns of skull modularity for four tribes in wrasses: hypsigenyines, julidines, cheilines, and scarines. The hypsigenyine and julidine groups showed the same two-module hypothesis for Labridae, whereas cheilines supported a four-module hypothesis with the three linkages as independent modules relative to the remainder of the skull. Scarines showed increased modularization of skull elements, where each bone is its own module. Diversification rates of modules show that linkage modules have evolved at a faster net rate of shape change than the remainder of the skull, with cheilines and scarines exhibiting the highest rate of evolutionary shape change. We developed a metric of linkage planarity and found the oral jaw linkage system to exhibit high planarity, while the rest position of the hyoid linkage system exhibited increased three dimensionality. This study shows a strong link between phenotypic evolution and biomechanical systems, with modularity influencing rates of shape change in the evolution of the wrasse skull.

Cardiopulmonary fitness is strongly associated with body cell mass and fat-free mass: The Study of Health in Pomerania (SHIP).

Peak oxygen uptake (VO2peak) is commonly indexed by total body weight (TBW) to determine cardiopulmonary fitness (CPF). This approach may lead to misinterpretation, particularly in obese subjects. We investigated the normalization of VO2peak by different body composition markers. We analyzed combined data of 3848 subjects (1914 women; 49.7%), aged 20-90, from two independent cohorts of the population-based Study of Health in Pomerania (SHIP-2 and SHIP-TREND). VO2peak was assessed by cardiopulmonary exercise testing. Body cell mass (BCM), fat-free mass (FFM), and fat mass (FM) were determined by bioelectrical impedance analysis. The suitability of the different markers as a normalization variable was evaluated by taking into account correlation coefficients (r) and intercept (α-coefficient) values from linear regression models. A combination of high r and low α values was considered as preferable for normalization purposes. BCM was the best normalization variable for VO2peak (r = .72; P ≤ .001; α-coefficient = 63.3 mL/min; 95% confidence interval [CI]: 3.48-123) followed by FFM (r = .63; P ≤ .001; α-coefficient = 19.6 mL/min; 95% CI: -57.9-97.0). On the other hand, a much weaker correlation and a markedly higher intercept were found for TBW (r = .42; P ≤ .001; α-coefficient = 579 mL/min; 95% CI: 483 to 675). Likewise, FM was also identified as a poor normalization variable (r = .10; P ≤ .001; α-coefficient = 2133; 95% CI: 2074-2191). Sex-stratified analyses confirmed the above order for the different normalization variables. Our results suggest that BCM, followed by FFM, might be the most appropriate marker for the normalization of VO2peak when comparing CPF between subjects with different body shape.

Is palivizumab effective as a prophylaxis of respiratory syncytial virus infections in cystic fibrosis patients? A meta-analysis.

BACKGROUND: Infections by respiratory syncytial virus (RSV) are more severe in patients with cystic fibrosis (CF), and many CF units use palivizumab as prophylaxis; however, information about palivizumab efficacy in CF patients is almost lacking. METHODS: A literature search up to December 2012 on the morbidity of RSV bronchiolitis in CF patients and on the safety and efficacy of palivizumab in those patients was performed. A random-effects meta-analysis was conducted for those studies meeting pre-specified search criteria. Historical controls were allowed. RESULTS: The number of patients who received palivizumab was 354 and the hospital admission rate was 0.018 (95% CI 0.0077-0.048). The corresponding number in the non-treated groups was 463 patients with an admission rate of 0.126 (95% CI 0.086-0.182) (Q=13.9; p<0.001). CONCLUSION: Palivizumab may have a role in the prevention of severe lower airway infection by RSV in CF patients.

Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosis-like phenotypes.

The term cystic fibrosis (CF)-like disease is used to describe patients with a borderline sweat test and suggestive CF clinical features but without two CFTR(cystic fibrosis transmembrane conductance regulator) mutations. We have performed the extensive molecular analysis of four candidate genes (SCNN1A, SCNN1B, SCNN1G and SERPINA1) in a cohort of 10 uncharacterized patients with CF and CF-like disease. We have used whole-exome sequencing to characterize mutations in the CFTR gene and these four candidate genes. CFTR molecular analysis allowed a complete characterization of three of four CF patients. Candidate variants in SCNN1A, SCNN1B, SCNN1G and SERPINA1 in six patients with CF-like phenotypes were confirmed by Sanger sequencing and were further supported by in silico predictive analysis, pedigree studies, sweat test in other family members, and analysis in CF patients and healthy subjects. Our results suggest that CF-like disease probably results from complex genotypes in several genes in an oligogenic form, with rare variants interacting with environmental factors.

Induced sputum cell count and cytokine profile in atopic and non-atopic children with asthma.

BACKGROUND AND AIM: Sputum induction is a semi-invasive technique used to detect and monitor airway inflammation. In this study, the cell profile, and Th1 and Th2 cytokine levels in induced sputum of asthmatic and healthy children (HC) are compared. METHODS: Sputum induction was performed in healthy and asthmatic children by inhalation of hypertonic saline solution. Differential cell count in the specimen obtained was carried out using optic microscopy. IFN-γ, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1ß, TNF-α, and IL-12p70 levels were determined in sputum sample supernatants by flow cytometry. RESULTS: Sputum induction was performed in 31 HC and 77 asthmatic children (60 atopic and 17 non-atopic asthma, NAA). Twenty-four samples were obtained in HC and 64 in patients. Median eosinophil count in atopic asthma (AA; 2%) was higher than in NAA (P = 0.02) or HC (P = 0.01). IL-4, IL-5, IFNγ, IL-2, and IL-12p70 concentrations were higher in AA than in NAA or HC. IL-8 was higher in asthmatic children (atopic and non-atopic) than in healthy ones. IL-10 was higher in the healthy group than in the AA group (P = 0.02). CONCLUSIONS: As compared to HC, the inflammatory profile in induced sputum of children with asthma showed an increase in proinflammatory cytokines. Concentrations of IL-10, an anti-inflammatory cytokine, were lower in children with AA than in HC.

[Value of nasal nitric oxide in the diagnosis of primary ciliary dyskinesia]. / Valor del óxido nítrico nasal en el diagnóstico de la discinesia ciliar primaria.

OBJECTIVE: The aim of this study is to report nasal nitric oxide (nNO) values in children with primary ciliary dyskinesia (PCD) and to compare them with nNO values in healthy children, asthmatic children, children with cystic fibrosis and children with post infectious bronchiectasis. PATIENTS AND METHODS: We determined nNO values in 9 children with PCD, 36 asthmatic children, 31 children with cystic fibrosis, 8 children with post infectious bronchiectasis and 37 healthy children. We compared nNO values between these different conditions and calculated sensitivity and specificity of nNO to diagnose PCD. RESULTS: All children with PCD - except one (nNO 348 ppb) - had nNO values below 112 ppb, mean 88 ppb (95%CI 9.6-166). The nNO mean was 898 ppb (95%CI 801-995) in healthy children, 1023 ppb (95%CI 911-1137) in asthmatic children, 438 ppb (95%CI 367-508) in cystic fibrosis children and 361 ppb (95%CI 252-470) in children with post infectious bronchiectasis. The mean concentration of nNO was lower (P<0.05) in PCD patients, compared to the other groups. The measurement of nasal NO in our study population showed, at a cut-off level of < or =112 ppb, a sensitivity of 88.9% and a specificity of 99.1% in the diagnosis of PCD [ROC 0.98 (95%CI 0.94-0.99); P<0.0001; probability ratio 95.1]. CONCLUSIONS: The measurement of nasal NO appears to be a useful tool for screening children for PCD, in which a cut-off level of < or =112 ppb suggests the disease, although nNO above 112 ppb does not exclude PCD.

[Sputum induction in children: Technical development]. / Inducción de esputo en niños: desarrollo técnico.

OBJECTIVE: To compare low and high flow nebulizers performance (total of samples) and its side effects on sputum induction in asthmatic children. PATIENTS AND METHODS: Sputum induction was performed by inhalation of a hypertonic saline solution at increasing concentrations (3%, 4% and 5%) using low flow (OMRON NE-U07; flow rate 1ml/min), or high flow (OMRON NE-U12; flow rate 3ml/min, and DeVilbiss Ultraneb 3000; flow rate 2.5ml/min) ultrasonic nebulizers. RESULTS: We performed 49 inductions in 49 patients from 7 to 15 years old (in 15 children we used a low flow nebulizer (Omron NE-U07) and in 34 children a high flow nebulizer (OMRON NEU12, 6 patients, and DeVilbiss Ultraneb 3000, 28 patients). We obtained 37 samples of which 36 had less than 20% of squamous cells, and 26 had a viability > or =60%. The test performance was higher with high-flow nebulizers, obtaining 85.3% of samples compared to 53% (p=0.04). A total of 69% of samples obtained with the high flow nebulizer were valid, compared to 62.5% (p=0.7) with the low flow nebulizers. With high flow rate nebulizers the incidence of cough (17.6%, p=0.08) and itchy eyes (0%, p=0.02) decreased with the low flow nebulizer (47% and 20% respectively), but bad taste (82.3%, p <0.001) and salivation (14.7%, p=0.3) increased. CONCLUSIONS: With high flow rate ultrasonic nebulizers we obtain a higher performance of the technique without an increase in significant side effects.

[Protocol for the diagnosis and follow up of patients with cystic fibrosis]. / Protocolo de diagnóstico y seguimiento de los pacientes con fibrosis quística.

Cystic fibrosis (CF) is the most common severe recessive genetic disease in Caucasians. During the last years, new therapies and aggressive management of the lung disease have contributed significantly to the increased life expectancy in CF patients. A review and update of CF diagnosis and management of lung disease are included. The sweat chloride test (SCT) remains the gold standard for CF diagnosis and should be performed properly. However, in a few patients SCT results may not be conclusive to clarify the CF diagnosis. Patients with CF should be followed up in specialist Units by an expert multidisciplinary expert applying standard clinical protocols and using lung function tests, and microbiological and imaging studies. An overview with the recommendations for treatment of early onset and chronic infections due to Pseudomonas aeruginosa, Staphylococcus aureus and other uncommon pathogens is included. Furthermore, the management of other aspects of CF lung disease and complications is provided, as well as the indications for lung transplantation. This document has been prepared by the members of the CF working group of the Spanish Paediatrics Pulmonary Society to provide an update to the earlier documents published in this Journal in 1999.

[Exogenous lipoid pneumonia]. / Neumonía lipoidea exógena.

The aspiration of lipoid material following the accidental ingestion of lipid formulations is the most frequent cause of exogenous lipoid pneumonia in paediatrics. The presence of cough, increasing dyspnea and chest pain, together with alveolar infiltrates in the chest radiography and the previous accidental intake of a lipid substance and vomiting should make us suspect this diagnosis. We present two cases of aspiration lipoid pneumonia in paediatric patients, with a different clinical presentation and radiological outcome, pointing out in one of them the appearance of pneumatoceles as a consequence of aspiration.

Bone marrow diffusion measures correlate with dementia severity in HIV patients.

BACKGROUND AND PURPOSE: Escalation in monocyte trafficking from the bone marrow into the brain may play a critical role in central nervous system injury and cognitive deterioration in patients with HIV infection. This study tested the hypothesis that the mean diffusivity is sensitive to marrow changes in HIV patients and that these quantitative imaging measurements correlate with the severity of dementia. METHODS: The mean diffusivity (MD), determined for clival and calvarial marrow regions, was compared in 11 HIV-infected patients and 9 control subjects. The imaging measurements were also evaluated for relationships with dementia severity and markers of disease progression (CD4 and viral load in plasma). RESULTS: The MD was significantly reduced in both clival and calvarial marrow in HIV-infected patients (P =.006). Diffusion measurements for clival (P =.02) and for calvarial (P =.03) regions were significantly correlated with the severity of dementia. CONCLUSION: The results of this investigation support the utility of diffusion strategies for monitoring the marrow and provide further evidence of a relationship between marrow status changes and neurologic progression in HIV patients.

Upregulation of COX-1 and COX-2 in nasal polyps in cystic fibrosis.

BACKGROUND: Since abnormalities in prostanoid metabolism occur in the lower airway of patients with cystic fibrosis (CF), it is likely that they could also be detected in the nose. METHODS: The degree of mRNA and protein expression of cyclo-oxygenase (COX) enzymes 1 (COX-1) and 2 (COX-2) was examined using quantitative reverse competitive polymerase chain reaction (RT-PCR) and Western blot analysis in the nasal polyps from 10 patients with CF, nasal polyps from 10 non-CF patients and 11 nasal mucosa specimens. The results are presented as 10(6) cDNA molecules/mug total RNA and the densitometric ratio between protein and beta-actin. RESULTS: COX-1 mRNA levels were significantly higher in CF nasal polyps (median 2.34, 25-75th percentiles 1.6-3.2) than in the nasal mucosa (0.78, 0.11-1.21), while there was no difference with non-CF nasal polyps (1.11, 0.80-3.15). COX-1 protein levels were significantly higher in CF nasal polyps (3.63, 2.71-4.27) than in nasal mucosa (1.55, 0.66-2.33) and non-CF nasal polyps (2.19, 1.72-3.68). COX-2 mRNA was significantly higher in CF nasal polyps (3.34, 2.42-7.05) than in nasal mucosa (1.69, 0.19-3.50). No differences were found in COX-2 mRNA expression between CF and non-CF polyps (1.38, 0.12-6.07). COX-2 protein levels were also significantly higher in CF nasal polyps (0.23, 0.04-0.34) than in non-CF nasal polyps (0.011, 0.009-0.016) or nasal mucosa (0.014, 0.014-0.016). CONCLUSIONS: Upregulation in the expression of COX-1 and COX-2 could explain the high production of prostanoids reported in CF. These findings raise questions regarding the potential use of selective or non-selective COX-2 non-steroidal anti-inflammatory treatment in CF.

Antimicrobial therapy for pulmonary pathogenic colonisation and infection by Pseudomonas aeruginosa in cystic fibrosis patients.

Pseudomonas aeruginosa colonisation has a negative effect on pulmonary function in cystic fibrosis patients. The organism can only be eradicated in the early stage of colonisation, while reduction of bacterial density is desirable during chronic colonisation or exacerbations. Monthly, or at least 3-monthly, microbiological culture is advisable for patients without previous evidence of P. aeruginosa colonisation. Cultures should be performed at least every 2-3 months in patients with well-established colonisation, and always during exacerbations or hospitalisations. Treatment of patients following the first isolation of P. aeruginosa, but with no clinical signs of colonisation, should be with oral ciprofloxacin (15-20 mg/kg twice-daily for 3-4 weeks) plus inhaled tobramycin or colistin (intravenous treatment with or without inhaled treatment can be used as an alternative), while patients with acute infection should be treated for 14-21 days with high doses of two intravenous antimicrobial agents, with or without an inhaled treatment during or at the end of the intravenous treatment. Maintenance treatment after development of chronic P. aeruginosa infection/colonisation (pathogenic colonisation) in stable patients (aged>6 years) should be with inhaled tobramycin (300 mg twice-daily) in 28-day cycles (on-off) or, as an alternative, colistin (1-3 million units twice-daily). Colistin is also a possible choice for patients aged<6 years. Treatment can be completed with oral ciprofloxacin (3-4 weeks every 3-4 months) for patients with mild pulmonary symptoms, or intravenously (every 3-4 months) for those with severe symptoms or isolates with ciprofloxacin resistance. Moderate and serious exacerbations can be treated with intravenous ceftazidime (50-70 mg/kg three-times-daily) or cefepime (50 mg/kg three-times-daily) plus tobramycin (5-10 mg/kg every 24 h) or amikacin (20-30 mg/kg every 24 h) for 2-3 weeks. Oral ciprofloxacin is recommended for patients with mild pulmonary disease. If multiresistant P. aeruginosa is isolated, antimicrobial agents that retain activity are recommended and epidemiological control measures should be established.

Age, apolipoprotein E4, and the risk of HIV dementia: the Hawaii Aging with HIV Cohort.

There are discrepant findings regarding the risk of HIV-associated dementia (HAD) relating to apolipoprotein E4, suggesting other factors may modulate risk. Furthermore, evidence suggests a changing phenotype of HAD in the era of highly active antiretroviral therapy (HAART), prompting a need to determine if new disease markers have emerged. In this analysis, APOE genotype was determined for 182 participants enrolled in the Hawaii Aging with HIV Cohort. After controlling for age and diabetes status, an independent risk of HAD relating to E4 was seen in older participants [OR=2.898 (1.031-8.244)] but not in younger participants [OR=0.373 (0.054-1.581)]. Several proposed mechanisms may underlie this association. Consideration of non-traditional risk factors for HAD in older HIV patients may yield new markers of disease in the era of HAART.

Experimental autoimmune encephalomyelitis (EAE): lesion visualization on a 3 Tesla clinical whole-body system after intraperitoneal contrast injection.

PURPOSE: To investigate the intravital visibility of CNS lesions in rats with experimental autoimmune encephalomyelitis (EAE), the animal correlate of multiple sclerosis, using a 3-Tesla (T) whole-body MR system. MATERIALS AND METHODS: Three healthy Dark Agouti (DA) rats and 16 DA rats with clinical signs of EAE were examined on a 3T whole body-system using a normal wrist coil. In total, 25 examinations were preformed using T2- and T1-weigthed images in transverse and sagittal orientation with a slice thickness of 2 mm or 1 mm (voxel size up to 0.2 x 0.2 x 1 mm). Sedation was achieved by intraperitoneal injection of ketamine and xylazine. In addition, T1-weighted images were obtained after the instillation of 1.0 ml of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.5 mmol/ml) into the peritoneal cavity. RESULTS: T2- and T1-weighted images of the brain and spinal cord with high spatial and contrast resolution could be obtained in all animals. The anatomical details of the olfactory bulb glomeruli, cerebellum foliae, ventricles and corpus callosum were clearly visible. The EAE lesions presented as hyperintense areas in T2-weighted images and could be demonstrated in all clinically affected animals by MRI and histologically verified. In total, the 16 affected rats had 28 cerebral and 2 spinal cord lesions (range 1 to 4, median 2). Contrast enhancement was noted in 12 animals and ranked as severe in ten and moderate in two cases. No adverse effects were noted due to sedation or intraperitoneal contrast injection. CONCLUSIONS: The intravital demonstration of cerebral and spinal cord EAE lesions in rats is possible on a 3T whole-body MR scanner using a normal wrist coil. Intraperitoneal injection of ketamine/xylazine and contrast agent is an easy, safe and effective procedure in rats.

[Comparative efficacy of oral deflazacort versus oral prednisolone in children with moderate acute asthma]. / Estudio comparativo de la eficacia del deflazacort frente a prednisolona en el tratamiento de la crisis asmática moderada.

OBJECTIVES: To assess the efficacy and tolerability of oral deflazacort versus oral prednisolone in acute moderate asthma in children. PATIENTS AND METHODS: We performed a prospective, randomized, parallel group trial of children aged 6 to 14 years old with a diagnosis of asthma who presented to the pediatric emergency department for moderate asthma exacerbation. All patients were administered short-acting beta2-adrenergic agonists. The intervention groups received either oral deflazacort (1.5 mg/kg) or prednisolone (1 mg/kg) for 7 days. The primary outcome measure was forced expiratory volume in 1 second (FEV1) and secondary outcome measures were pulmonary symptom score index, peak expiratory flow rate (PEFR), hospitalization rate and the use of rescue beta2-agonists. Patients were evaluated at the start of treatment (visit 1), on day 2 (visit 2) and on day 7 (visit 3). RESULTS: Of the 54 children enrolled, two were hospitalized on visit 2 (one from each group). Baseline clinical data were similar in both groups: FEV1: 53 and 51 %; bronchodilator test: 119 and 121 %; PEFR: 169 and 165 L/min; symptom score: 6 and 6.5 for the deflazacort and prednisolone groups, respectively. On visit 2, all measures improved: FEV1: 122.2 and 126.5 % (p < 0.05); PEFR: 164 and 149 L/min (p < 0.05); symptom score: -4.4 and -3.8 (p < 0.05), without significant differences between groups. On visit 3 all variables continued to show improvement: FEV1: 133.2 and 132.5 % (p < 0.05); PEFR: 1115.7 and 187.6 L/min (p < 0.05); symptom score: -5.4 and -5.9 (p < 0.05), without significant differences between groups. No adverse effects were reported. CONCLUSIONS: Deflazacort and prednisolone show similar efficacy in improving pulmonary function and in producing clinical improvement in the management of acute moderate asthma in children.

Efficient gene transfer into human monocyte-derived macrophages using defective lentiviral vectors.

Gene therapy is a promising approach for the treatment of neurological disorders. However, current approaches to gene transfer in the central nervous system (CNS) are limited by the lack of effective, but non-invasive methods to deliver transgenes across the blood-brain barrier (BBB). In an effort to begin to explore the use of migratory monocytes as vehicles for delivery of therapeutic and antiviral genes into the CNS, we have utilized three HIV-based transfer vectors encoding cis-acting elements but lacking either structural genes (gag/pol and env), most accessory genes (vif, vpr and nef) and/or rev. These defective lentiviral vectors (DLV) encode the green fluorescent protein (GFP), display potent antiviral activity in CD4+ lymphocytes and can be mobilized by wild-type HIV-1 DLV were generated by transient transfection of 293T cells. Vector titers ranged from 4.2-6.6 x 10(6) infectious units (IU)/ml prior to concentration (by ultracentrifugation) and were equal to or higher than 1 x 10(9) IU/ml after concentration. Primary human monocyte-derived macrophages (MDM) were exposed to DLV resulting in efficiencies of transduction ranging from 14 to 26%. GFP expression in transduced MDM remained stable for more than 8 weeks without apparent cytopathic effect. Given the previously reported antiviral activities of these DLV and their lack of cytopathic effects on primary MDM, it may be possible to use these vectors to inhibit HIV-1 replication within the CNS.

Lung transplantation in young infants with interstitial pneumonia.

OBJECTIVES: We describe our experience with infants suffering from interstitial pneumonia referred for lung transplantation. METHODS: From April 1998 to December 2000, three infants were admitted to our lung transplantation program: a 9-month-old girl (patient 1) suffering from surfactant protein C deficiency who had high oxygen requirements (fraction of inspired oxygen: 70% to 90%), and two boys, ages 2 (patient 2) and 9 months (patient 3), who were ventilator-dependent due to chronic pneumonitis of infancy. RESULTS: Patients were transplanted at the age of 5 months (patient 2) and 13 months (patients 1 and 3) at 87 to 105 days after being accepted for lung transplantation. All cases underwent a sequential double lung transplant on cardiopulmonary bypass. The immunosuppressive regime included tacrolimus, prednisone, and azathioprine. Patients 2 and 3 also received basiliximab. Two cases suffered a mild rejection episode that responded to high-dose steroids. Patient 2 was ventilator-dependent for 8 months after transplant, owing to severe bronchomalacia and left main bronchus stenosis. Bronchial stenosis resolved after pneumatic dilatation and endobronchial stenting. This patient also presented with a pulmonary artery anastomosis stricture that required percutaneous balloon dilatation. All three patients are at home, carrying out normal activities for their age, with no respiratory symptoms after a period of 8 to 29 months of follow-up. CONCLUSIONS: Interstitial pneumonia of infancy is a rare disease with a bad prognosis and no specific treatment; therefore, lung transplantation represents a good therapeutic option for these infants.

Retinol measurements and retinoid receptor gene expression in patients with multiple sclerosis.

Treatment with interferon (IFN)-beta1a has been associated with decreased disease activity in patients with multiple sclerosis (MS). In several biological systems, type 1 IFNs and retinoids have been demonstrated to have synergistic effects. In these studies, we measured blood and cerebrospinal fluid (CSF) retinol levels and naïve and memory T-helper cell subset percentages in samples from a group of patients with MS. We also examined retinol receptor expression in peripheral blood cells from MS patients with or without a history of prior treatment with IFN-beta1a. The mean plasma retinol level for untreated relapsing-remitting (RR) MS patients was lower than for patients with noninflammatory neurological disease. Among IFN-beta1a-treated RR patients, mean levels were slightly higher than for RR patients not on treatment Lower plasma retinol levels among the MS patents studied were associated with higher CSF retinol index measurements--a measure that was calculated to correct for nonspecific leakage of retinol from blood into CSF. Far the MS samples examined, there was a borderline statstically significant direct correlation between CSF retinol index measurements and CSF memory T-helper cell percentages. Examination of peripheral blood from untreated RR patents for retinoid receptor mRNA expression revealed the expression of the retinoic add receptor (RAR)-alpha, RAR-gamma, and retinoic X receptor (RXR)-alpha receptor subtypes. For RR patients on IFN-beta1a therapy, expression of the some RAR subtypes was noted as well as expression of RXR-beta and RXR-gamma. These studies suggest an association between plasma retinol levels and clincal disease activity in patents with MS and that treatment with IFN-beta1a may be associated with activation of specific retnoid receptor subtypes.