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1.
Brain Spine ; 4: 102822, 2024.
Article En | MEDLINE | ID: mdl-38831935

Introduction: Technical advances and the increasing role of interdisciplinary decision-making may warrant formal definitions of expertise in surgical neuro-oncology. Research question: The EANS Neuro-oncology Section felt that a survey detailing the European neurosurgical perspective on the concept of expertise in surgical neuro-oncology might be helpful. Material and methods: The EANS Neuro-oncology Section panel developed an online survey asking questions regarding criteria for expertise in neuro-oncological surgery and sent it to all individual EANS members. Results: Our questionnaire was completed by 251 respondents (consultants: 80.1%) from 42 countries. 67.7% would accept a lifetime caseload of >200 cases and 86.7% an annual caseload of >50 as evidence of neuro-oncological surgical expertise. A majority felt that surgeons who do not treat children (56.2%), do not have experience with spinal fusion (78.1%) or peripheral nerve tumors (71.7%) may still be considered experts. Majorities believed that expertise requires the use of skull-base approaches (85.8%), intraoperative monitoring (83.4%), awake craniotomies (77.3%), and neuro-endoscopy (75.5%) as well as continuing education of at least 1/year (100.0%), a research background (80.0%) and teaching activities (78.7%), and formal interdisciplinary collaborations (e.g., tumor board: 93.0%). Academic vs. non-academic affiliation, career position, years of neurosurgical experience, country of practice, and primary clinical interest had a minor influence on the respondents' opinions. Discussion and conclusion: Opinions among neurosurgeons regarding the characteristics and features of expertise in neuro-oncology vary surprisingly little. Large majorities favoring certain thresholds and qualitative criteria suggest a consensus definition might be possible.

2.
J Family Med Prim Care ; 12(6): 1137-1144, 2023 Jun.
Article En | MEDLINE | ID: mdl-37636193

Background: Social media (SM) usage is on the rise among health professionals at all levels to align with the emerging digital and SM era. e-Professionalism is described as attitudes and actions that resemble traditional professionalism paradigms but are expressed through digital media. Although there are a number of studies conducted in the past several years measuring e-professionalism of medical and dental professionals, there is no validated scale to assess the level of e-professionalism among medical and dental professionals in Saudi Arabia. Therefore, this study aimed to assess attitudes toward e-professionalism among medical and dental professionals in Saudi Arabia using the SMePROF-S scale. Methods: This cross-sectional study recruited 338 medical and dental students and practitioners from 20 cities in Saudi Arabia to complete an online SMePROF-S self-reported questionnaire measuring attitudes about e-professionalism. Results: Among participants, 31.66% believed that it is acceptable to communicate with patients through SM, but only 16.86% agreed with communicating via personal SM account messaging. Many participants (35.80%-50%) fear that SM use can cause problems with getting hired, people making inaccurate assumptions and perceptions, and job losses. There were 31.36% who believed that sharing patient information without consent is acceptable. The majority (63.02%-63.31%) do not believe that medical/dental professionals should be barred from using SM, and 40.53% believe that schools/organizations have no right to interfere with their online activities. Only 22.19% believed that SM use removed professional protections from the public. A few statements were statistically different by specialty and gender. Conclusion: There is a variability of attitudes about e-professionalism among medical and dental professionals in Saudi Arabia, with some alarming issues requiring national guidelines to ensure patient rights, privacy, and confidentiality.

3.
Cureus ; 15(3): e35776, 2023 Mar.
Article En | MEDLINE | ID: mdl-37025729

Diffuse capillary malformation with overgrowth (DCMO) is a rare condition that is characterized by capillary malformation and soft tissue hypertrophy. Here we report the case of a one-year-old male child with no past medical history who presented with skin lesions persistent since birth and associated with no symptoms. There were widespread non-scaly reticulated erythematous patches all over his body, including the abdominal wall. The circumference of the right calf and mid-thigh was 13 cm and 20 cm respectively whereas the circumference of the left calf and mid-thigh was 11 cm and 18 cm respectively. The length of both lower extremities was similar. There was also syndactyly of the right second and third toes. Differential diagnoses include cutis marmorata telangiectatica congenita (CMTC), DCMO, and macrocephaly-capillary malformation (M-CM) syndrome. Based on clinical features, the patient was diagnosed with DCMO. He was put under follow-up by pediatric orthopedics for periodic monitoring of growth asymmetry.

4.
Cureus ; 15(2): e34816, 2023 Feb.
Article En | MEDLINE | ID: mdl-36915846

Background Foreign body aspiration (FBA) is a life-threatening event and one of the most common causes of mortality in children. As it has different clinical presentations, parental knowledge is essential for early management to prevent complications. Objectives This study was designed to assess the knowledge and practices relating to FBA in children among parents living in Makkah city, Saudi Arabia. Methods An online questionnaire was designed using Google Forms (Google LLC, Mountain View, California, United States) and distributed in October 2022 among parents living in Makkah city. After data collection, an appropriate statistical analysis was conducted. Results A total of 1087 parents enrolled in this study; 63.9% were women and the majority were married 93%. Additionally, 52% of the parents had at least three children. Moreover, 17.6% had an experience of a child having aspirated a foreign body once. The Internet was the most popular source of information on FBA (43.5%). Furthermore, the parents had poor levels of knowledge and practices related to FBA (65.4% and 78.6%, respectively). Conclusion This study reported that parental levels of knowledge of FBA and FBA practices were inadequate. There is a need to increase awareness, which will lead to better outcomes.

5.
Cureus ; 15(1): e33706, 2023 Jan.
Article En | MEDLINE | ID: mdl-36788915

Acanthosis nigricans (AN) is a common chronic disorder that is characterized by velvety-like, hyperpigmented, hyperkeratotic plaques, typically in intertriginous areas. However, atypical presentations have been reported. Here we present a five-year-old boy presented with a one-year history of asymptomatic slowly progressing skin lesions. He is a known case of type 1 diabetes mellites on insulin treatment, otherwise healthy. The review of systems was unremarkable. No similar case was found in the family. Skin examination revealed multiple tiny non-scaly brownish papules on the medial aspects of the upper thighs, bilaterally. Differential diagnosis included skin tags, viral warts, and dermatosis papulose nigra (DPN). Dermoscopic findings revealed a velvety-like appearance on the papules and the normal skin surrounding the papules. A 2-mm punch skin biopsy of the papule revealed papillomatosis of the epidermis, and the granular layer was normal. The dermis was normal. On the basis of the above clinicopathological findings, specifically the velvety texture of the normal skin surrounding the papules, the patient was diagnosed with ANs. The parent was reassured, and we started the patient on daily tretinoin cream.

6.
J Pharm Biomed Anal ; 190: 113529, 2020 Oct 25.
Article En | MEDLINE | ID: mdl-32841780

Despite the fact that more than 90% of vitamin D analysis are performed using immuno-enzymatic techniques, it is liquid chromatography coupled with tandem mass spectrometry that is currently the reference method. It allows for specific and selective analysis of all relevant vitamin D metabolites from a variety of biological materials, including serum or a dried blood spot. This paper presents development of a fast, cheap and high-throughput method of serum sample preparation using protein precipitation. For this purpose, organic solvent is used. Several substances were tested, including acetonitrile, methanol and their mixtures with zinc sulfate. However, the highest recovery values for the vitamin D metabolites were obtained for acetonitrile, with an organic solvent to serum ratio of 8:1. The preparation of a sample is carried out in 96-well plates and takes an hour and a half, together with a derivatization reaction using Cookson-type reagent 4-(4'-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione. Due to the fact that vitamin D metabolites are bound to proteins, the relationship between the content of organic solvent in the sample preparation process and their release from the protein complex was examined. The results indicate that the organic solvent content should be 30-70% in order to completely release the tested compounds from the proteins. In addition, the developed chromatographic method has eliminated false positive signals for the 24,25(OH)2D3 metabolite. Total analysis time is 5.5 min., while maintaining resolution necessary to separate the analyzed compounds.


Tandem Mass Spectrometry , Vitamin D , Chromatography, Liquid , Indicators and Reagents , Limit of Detection
7.
Analyst ; 144(1): 299-309, 2018 Dec 17.
Article En | MEDLINE | ID: mdl-30403208

There are two forms of vitamin D which are essential to the human body, i.e. vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). The inactive metabolites of vitamin D are commonly used for quantitative analysis because of their longer half-life, stability, and relatively high blood concentrations. This paper presents the development of a high-throughput and sensitive method for determining four vitamin D metabolites in dried blood spots using liquid chromatography coupled with tandem mass spectrometry. This method allows for the determination of 25(OH)D2 and 25(OH)D3 concentrations, as well as the epimeric form 3-epi-25(OH)D3 and 24,25(OH)2D3. The analyzed material is capillary blood taken from the fingertip, deposited on filter paper. Four different chromatographic columns were tested to separate all compounds, in particular, the epimeric form. The column of choice was F5 (Phenomenex, Torrance, CA, USA). In order to prove the consistency between the results for DBS, used as an alternative biological matrix, and serum, comparative studies of these two materials were carried out in nearly 100 individuals. The results indicated their positive correlation. The evaluation of short-term stability of metabolites in DBS within the month showed no change in metabolite concentration. During the validation, the impact of the matrix on the ionization of the tested compounds was evaluated. Capillary blood and venous blood collected for different anticoagulants were also compared. The smallest differences in the results were obtained for citrate. In order to achieve a limit of quantitation of 0.2 ng ml-1, sample preparation involved derivatization using a Cookson-type reagent, 4-(4'-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD).


Dried Blood Spot Testing/methods , Hydroxycholecalciferols/analysis , Aniline Compounds/chemistry , Chromatography, Liquid/methods , Female , High-Throughput Screening Assays/methods , Humans , Hydroxycholecalciferols/chemistry , Limit of Detection , Male , Stereoisomerism , Tandem Mass Spectrometry/methods , Triazoles/chemistry
8.
J Physiol Pharmacol ; 68(2): 209-214, 2017 Apr.
Article En | MEDLINE | ID: mdl-28614770

Phosphate-activated glutaminase (GA), a ubiquitous glutamine-metabolizing enzyme, is encoded by two genes, GLS and GLS2. In mammalian cancers, GLS isoforms are perceived as molecules promoting cell proliferation and invasion, whereas the role of GLS2 isoforms seems to be more complex and cell type-specific. Previous studies have shown abundance of GLS and lack of GLS2 transcripts in T98G human glioblastoma (GBM) cell line and patient-derived GBM. Transfection with GAB sequence, the whole GLS2 cDNA transcript, suppressed malignant phenotype of T98G cells. Microarray analysis revealed upregulation of GATA3, the product of which has been implicated in suppressing growth of some peripheral cancers. In this study we confirmed a significant upregulation of GATA3 expression in the transfected cells both at mRNA and protein level. Considerable expression of GATA3 was also observed in GBM tissues (previously shown as not expressing GLS2), while only traces or no GATA3 was detected in (GLS2-expressing) non-tumorigenic brain samples. In conclusion, while mechanistic relation between GAB and GATA3 expression is evident following in vitro manipulation of GBM cell line, it does not appear to be an intrinsic property of GBM nor non-tumorigenic brain tissue.


Brain Neoplasms/genetics , GATA3 Transcription Factor/genetics , Glioblastoma/genetics , Glutaminase/genetics , Adult , Aged , Brain/metabolism , Brain Neoplasms/metabolism , Cell Line, Tumor , Female , GATA3 Transcription Factor/metabolism , Glioblastoma/metabolism , Humans , Male , Middle Aged
9.
Folia Neuropathol ; 53(1): 41-51, 2015.
Article En | MEDLINE | ID: mdl-25909874

Trauma in spinal cord injury often results in massive damage to the white matter and in damage to myelin that results in a severe phagocyte-rich infiltration apparently directed at removing immunologically toxic myelin debris. In the epidural balloon crush injury to the rat cranial thoracic spinal cord, the dorsal column was crushed, which at one week post-op resulted in its obliteration by a severe infiltration by a virtually pure population of macrophages that internalized all damaged myelin. A week-long subdural infusion of dexamethasone, a stable synthetic corticosteroid, resulted in remarkable inhibition of the macrophage infiltration of the crush cavity and in the lack of removal of myelin debris by phagocytosis. In this study we demonstrated that spinal cord injury results in a severe inflammatory response directed at massively damaged myelin, and we inhibited this response with a subdural infusion of a powerful anti-inflammatory drug, dexamethasone.


Dexamethasone/administration & dosage , Disease Models, Animal , Myelitis/prevention & control , Nerve Fibers, Myelinated/drug effects , Spinal Cord Injuries/drug therapy , Subdural Space , Animals , Female , Male , Myelitis/etiology , Myelitis/pathology , Nerve Fibers, Myelinated/pathology , Rats , Rats, Long-Evans , Spinal Cord Injuries/complications , Spinal Cord Injuries/pathology
10.
Article En | MEDLINE | ID: mdl-24480328

The main aim of the present study was to develop a method for the separation of 5'-monophosphate nucleotides with the use of ion chromatography. Novel dendrimeric stationary phases were used for this purpose. The effects exerted by the type of anion-exchanger support (silica or polymeric) and the number of stationary phase layers on nucleotide retention were studied. A silica-based dendrimeric anion-exchanger was most suitable for analyzing the studied compounds. An increase in the number of layers enhanced nucleotide retention inside the column. The separation efficiency of the studied compounds was tested at various concentrations of the mobile phase buffer. At higher phosphate buffer concentrations, nucleotide resolutions were achieved in 6min. Three commercially available infant milk formulas were analyzed to verify the applicability of the studied method. Solid phase extraction was used for sample cleanup and concentration. The limit of quantification of nucleotides was 0.40µg/ml, and the method was linear in the concentration range of 0.40-20.6µgml(-1.)


Chromatography, Ion Exchange/methods , Dendrimers/chemistry , Infant Formula/chemistry , Nucleotides/analysis , Chromatography, Ion Exchange/instrumentation , Humans , Hydrogen-Ion Concentration , Infant , Linear Models , Reproducibility of Results , Sensitivity and Specificity
11.
Sex Disabil ; 31(2): 141-153, 2013 Jun.
Article En | MEDLINE | ID: mdl-23704801

Sexual concerns are known to be common in women suffering from multiple sclerosis (MS) but definite data on the prevalence of particular sexual dysfunctions (SD) remain unclear. Previous studies brought inconsistent findings and rely on small groups of patients or use of unvalidated assessment methods. The aim of this research was to evaluate the prevalence of SD in women with MS using validated clinimetric scales. 137 female inpatients with MS diagnosis were interviewed, completed The Female Sexual Function Questionnaire SFQ28 and underwent neurological assessment. Only 2.2 % of patients had ever discussed their sexual concerns with a physician. 70.1 % reported sexual activity. At least one SD could be found in 82.5 % of patients, hypoactive sexual desire (57.7 %), arousal dysfunction (decreased genital sensation in 47.3 %, decreased lubrication in 48.4 %, decreased subjective arousal in 45.2 %) and orgasmic dysfunction (39.8 %) being the most probable. SD were less likely in women who assessed their relationship positively but more common in older patients and those who had a positive history of depression. The prevalence of SD was higher comparing to the majority of studies by other authors. In conclusion, SD are very common in female patients with MS and permanently overlooked by medical professionals. Therefore, the assessment of sexual function should be implemented in all patients after the diagnosis of MS. Further research is needed for better understanding of the sexuality of this particular population in order to establish targets for therapeutic intervention.

12.
Cerebellum ; 12(3): 418-28, 2013 Jun.
Article En | MEDLINE | ID: mdl-23090211

Although ataxia is by definition the prominent symptom of ataxia disorders, there are various neurological signs that may accompany ataxia in affected patients. Reliable and quantitative assessment of these signs is important because they contribute to disability, but may also interfere with ataxia. Therefore we devised the Inventory of Non-Ataxia Signs (INAS), a list of neurological signs that allows determining the presence and severity of non-ataxia signs in a standardized way. INAS underwent a rigorous validation procedure that involved a trial of 140 patients with spinocerebellar ataxia (SCA) for testing of inter-rater reliability and another trial of 28 SCA patients to assess short-term intra-rater reliability. In addition, data of the ongoing EUROSCA natural history study were used to determine the reproducibility, responsiveness and validity of INAS. Inter-rater reliability and short-term test-retest reliability was high, both for the total count and for most of the items. However, measures of responsiveness, such as the smallest detectable change and the clinically important change were not satisfactory. In addition, INAS did not differentiate between subjects that were subjectively stable and those that worsened in the 2-year observation period. In summary, INAS and INAS count showed good reproducibility, but unsatisfactory responsiveness. The present analysis and published data from the EUROSCA natural history study suggest that INAS is a valid measure of extracerebellar involvement in progressive ataxia disorders. As such, it is useful as a supplement to the measures of ataxia, but not as a primary outcome measure in future interventional trials.


Neurologic Examination , Severity of Illness Index , Spinocerebellar Ataxias/diagnosis , Area Under Curve , Europe , Female , Humans , Longitudinal Studies , Male , Psychometrics , Reproducibility of Results , Spinocerebellar Ataxias/classification , Spinocerebellar Ataxias/genetics , Statistics as Topic
13.
J Physiol Pharmacol ; 63(5): 457-62, 2012 Oct.
Article En | MEDLINE | ID: mdl-23211299

Cyclic adenosine monophosphate (cAMP) levels in medial prefrontal cortex (mPFC) pyramidal neurons are altered in neuropsychiatric disorders. cAMP is a component of the transduction pathways involved in the control of ionic channels by metabotropic receptors. The purpose of this study was to determine whether cAMP modifies the activity of the G protein-dependent inward rectifier K(+) (GIRK)-like channel current in the mPFC pyramidal neurons of 3-week-old rats. Channel currents were recorded in a patch clamp cell-attached configuration. Membrane-permeable adenylyl cyclase activator forskolin (10 µM) and membrane-permeable protein kinase A (PKA) activator 8-Br-cAMP (100 µM) were found to significantly decrease the open probability (Po) of the GIRK-like channels. Conversely, selective protein kinase A inhibitors: H-89 (10 µM) and KT5720 (0.5 µM) increased the open probability of the GIRK-like channels. Also, the effect of forskolin was tested after preincubation of the neurons with the PKA inhibitor (KT5720). The application of forskolin, despite PKA inhibition, significantly decreased the Po of the GIRK-like channels. This finding suggested that GIRK-like channel current activity might also be inhibited by cAMP in a PKA-independent manner. A compound, 8CPT-2Me-cAMP (10 µM), which is a specific activator of the Epac protein, which in turn is another intracellular target of cAMP, was also found to inhibit GIRK-like channel activity. We conclude that the constitutive activity of neuronal GIRK-like channel currents is inhibited by cAMP. We suggest that PKA and Epac might be components of the transduction pathway between cAMP and the GIRK channels.


Cyclic AMP/physiology , G Protein-Coupled Inwardly-Rectifying Potassium Channels/physiology , Prefrontal Cortex/physiology , Pyramidal Cells/physiology , 8-Bromo Cyclic Adenosine Monophosphate/pharmacology , Animals , Colforsin/pharmacology , Cyclic AMP-Dependent Protein Kinases/physiology , In Vitro Techniques , Male , Rats , Rats, Wistar
14.
Neurology ; 77(11): 1035-41, 2011 Sep 13.
Article En | MEDLINE | ID: mdl-21832228

OBJECTIVE: To obtain quantitative data on the progression of the most common spinocerebellar ataxias (SCAs) and identify factors that influence their progression, we initiated the EUROSCA natural history study, a multicentric longitudinal cohort study of 526 patients with SCA1, SCA2, SCA3, or SCA6. We report the results of the 1- and 2-year follow-up visits. METHODS: As the primary outcome measure we used the Scale for the Assessment and Rating of Ataxia (SARA, 0-40), and as a secondary measure the Inventory of Non-Ataxia Symptoms (INAS, 0-16) count. RESULTS: The annual increase of the SARA score was greatest in SCA1 (2.18 ± 0.17, mean ± SE) followed by SCA3 (1.61 ± 0.12) and SCA2 (1.40 ± 0.11). SARA progression in SCA6 was slowest and nonlinear (first year: 0.35 ± 0.34, second year: 1.44 ± 0.34). Analysis of the INAS count yielded similar results. Larger expanded repeats and earlier age at onset were associated with faster SARA progression in SCA1 and SCA2. In SCA1, repeat length of the expanded allele had a similar effect on INAS progression. In SCA3, SARA progression was influenced by the disease duration at inclusion, and INAS progression was faster in females. CONCLUSIONS: Our study gives a comprehensive quantitative account of disease progression in SCA1, SCA2, SCA3, and SCA6 and identifies factors that specifically affect disease progression.


Disease Progression , Machado-Joseph Disease/classification , Machado-Joseph Disease/diagnosis , Spinocerebellar Ataxias/classification , Spinocerebellar Ataxias/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Follow-Up Studies , Humans , Longitudinal Studies , Machado-Joseph Disease/epidemiology , Male , Middle Aged , Prospective Studies , Retrospective Studies , Spinocerebellar Ataxias/epidemiology , Young Adult
15.
Neurology ; 74(8): 678-84, 2010 Feb 23.
Article En | MEDLINE | ID: mdl-20177122

OBJECTIVE: To determine the longitudinal metric properties of recently developed clinical assessment tools in spinocerebellar ataxia (SCA). METHODS: A subset of 171 patients from the EUROSCA natural history study cohort (43 SCA1, 61 SCA2, 37 SCA3, and 30 SCA6) were examined after 1 year of follow-up. Score changes and effect size indices were calculated for clinical scales (Scale for the Assessment and Rating of Ataxia [SARA], Inventory of Non-Ataxia Symptoms [INAS]), functional tests (SCA Functional Index [SCAFI] and components), and a patient-based scale for subjective health status (EQ-5D visual analogue scale [EQVAS]). Responsiveness was determined in relation to the patient's global impression (PGI) of change and reproducibility described as retest reliability for the stable groups and smallest detectable change. RESULTS: Within the 1-year follow-up period, SARA, INAS, and SCAFI but not EQVAS indicated worsening in the whole group and in the groups with subjective (PGI) worsening. SCAFI and its 9-hole pegboard (9HPT) component also deteriorated in the stable groups. Standardized response means were highest for 9HPT (-0.67), SARA (0.50), and SCAFI (-0.48) with accordingly lower sample size estimates of 143, 250, or 275 per group for a 2-arm interventional trial that aims to reduce disease progression by 50%. SARA and EQVAS performed best to distinguish groups classified as worse by PGI. All scales except EQVAS reached the criterion for retest reliability. CONCLUSION: While both the Scale for the Assessment and Rating of Ataxia and the SCA Functional Index (SCAFI) (and its 9-hole pegboard component) had favorable measurement precision, the clinical relevance of SCAFI and 9-hole pegboard score changes warrants further exploration. The EQ-5D visual analogue scale proved insufficient for longitudinal assessment, but validly reflected patients' impression of change.


Severity of Illness Index , Spinocerebellar Ataxias/diagnosis , Area Under Curve , Disease Progression , Health Status , Humans , Patient Selection , Quality of Life , Reproducibility of Results , Surveys and Questionnaires
16.
Neurology ; 71(7): 486-92, 2008 Aug 12.
Article En | MEDLINE | ID: mdl-18695159

OBJECTIVE: To evaluate the usefulness of functional measures in patients with spinocerebellar ataxia (SCA). METHODS: We assessed three functional measures-8 m walking time (8MW), 9-hole peg test (9HPT), and PATA repetition rate-in 412 patients with autosomal dominant SCA (genotypes 1, 2, 3, and 6) in a multicenter trial. RESULTS: While PATA rate was normally distributed (mean/median 21.7/20.5 per 10 s), the performance times for 8MW (mean/median 10.8/7.5 s) or 9HPT (mean/median 47.2/35.0 s in dominant, 52.2/37.9 s in nondominant hand) were markedly skewed. Possible learning effects were small and likely clinically irrelevant. A composite functional index (SCAFI) was formed after appropriate transformation of subtest results. The Z-scores of each subtest correlated well with the Scale for the Assessment and Rating of Ataxia (SARA), the Unified Huntington's disease Rating Scale functional assessment, and disease duration. Correlations for SCAFI with each of these parameters were stronger (Pearson r = -0.441 to -0.869) than for each subtest alone. Furthermore, SCAFI showed a linear decline over the whole range of disease severity, while 9HPT and 8MW had floor effects with respect to SARA. Analysis of possible confounders showed no effect of genotype or study site and only minor effects of age for 8MW. CONCLUSION: The proposed functional measures and their composite SCAFI have favorable properties to assess patients with spinocerebellar ataxia.


Disability Evaluation , Motor Skills/physiology , Spinocerebellar Ataxias/physiopathology , Female , Humans , Male , Middle Aged
17.
Neurology ; 71(13): 982-9, 2008 Sep 23.
Article En | MEDLINE | ID: mdl-18685131

OBJECTIVE: To identify factors that determine disease severity and clinical phenotype of the most common spinocerebellar ataxias (SCAs), we studied 526 patients with SCA1, SCA2, SCA3. or SCA6. METHODS: To measure the severity of ataxia we used the Scale for the Assessment and Rating of Ataxia (SARA). In addition, nonataxia symptoms were assessed with the Inventory of Non-Ataxia Symptoms (INAS). The INAS count denotes the number of nonataxia symptoms in each patient. RESULTS: An analysis of covariance with SARA score as dependent variable and repeat lengths of the expanded and normal allele, age at onset, and disease duration as independent variables led to multivariate models that explained 60.4% of the SARA score variance in SCA1, 45.4% in SCA2, 46.8% in SCA3, and 33.7% in SCA6. In SCA1, SCA2, and SCA3, SARA was mainly determined by repeat length of the expanded allele, age at onset, and disease duration. The only factors determining the SARA score in SCA6 were age at onset and disease duration. The INAS count was 5.0 +/- 2.3 in SCA1, 4.6 +/- 2.2 in SCA2, 5.2 +/- 2.5 in SCA3, and 2.0 +/- 1.7 in SCA6. In SCA1, SCA2, and SCA3, SARA score and disease duration were the strongest predictors of the INAS count. In SCA6, only age at onset and disease duration had an effect on the INAS count. CONCLUSIONS: Our study suggests that spinocerebellar ataxia (SCA) 1, SCA2, and SCA3 share a number of common biologic properties, whereas SCA6 is distinct in that its phenotype is more determined by age than by disease-related factors.


Machado-Joseph Disease/classification , Machado-Joseph Disease/diagnosis , Spinocerebellar Ataxias/classification , Spinocerebellar Ataxias/diagnosis , Adult , Diagnosis, Differential , Female , Germany/epidemiology , Humans , Machado-Joseph Disease/epidemiology , Male , Middle Aged , Severity of Illness Index , Spinocerebellar Ataxias/epidemiology
18.
Neuroscience ; 155(1): 53-63, 2008 Jul 31.
Article En | MEDLINE | ID: mdl-18571868

Pyramidal neurons of the medial prefrontal cortex (mPFC) exhibit dopamine-dependent prolonged depolarization, which may lead to persistent activity. Persistent activation of prefrontal cortex neurons has been proposed to underlie the working memory process. The purpose of our study was to test the hypothesis that activation of D(1) dopamine receptors leads to inhibition of G protein-dependent inward rectifier K(+) (GIRK) channels, thereby supporting the prolonged depolarization of mPFC pyramidal neurons. Experiments were performed on 3-week-old rats. GIRK-like channel currents recorded from pyramidal neurons showed the following properties at -75 mV: open probability (NPo), 2.5+/-0.3 x 10(-3); mean open time, 0.53+/-0.05 ms; and conductance, 29.9+/-1.6 pS (n=60). The channel currents were strongly inward-rectified. GIRK channel currents were reversibly inhibited by the D(1) agonists SKF 38393 (10 microM) and SKF 81297 (10 microM). This inhibition was abolished by prior application of a dopamine receptor antagonist and by application of the membrane-permeable protein kinase C inhibitors chelerythrine chloride (3 microM) and calphostin C (10 microM). It was also found that the application of D(1) dopamine receptor agonists or GIRK channel inhibitors evoked depolarization of mPFC pyramidal neurons in rats. Moreover, prior application of a GIRK channel blocker eliminated the depolarizing effect of D(1) agonists. We conclude that activation of D(1) dopamine receptors may lead to inhibition of GIRK channel currents that may, in turn, lead to the prolonged depolarization of mPFC pyramidal neurons in juvenile rats.


G Protein-Coupled Inwardly-Rectifying Potassium Channels/physiology , Prefrontal Cortex/cytology , Pyramidal Cells/physiology , Receptors, Dopamine D1/physiology , Analysis of Variance , Animals , Bee Venoms/pharmacology , Dopamine Agents/pharmacology , Dose-Response Relationship, Radiation , Drug Interactions , Electric Stimulation/methods , Enzyme Inhibitors/pharmacology , In Vitro Techniques , Male , Naphthalenes/pharmacology , Patch-Clamp Techniques/methods , Potassium Channel Blockers/pharmacology , Pyramidal Cells/drug effects , Pyramidal Cells/radiation effects , Rats , Rats, Wistar , Tetradecanoylphorbol Acetate/analogs & derivatives , Tetradecanoylphorbol Acetate/pharmacology , Time Factors
19.
J Physiol Pharmacol ; 59 Suppl 6: 615-21, 2008 Dec.
Article En | MEDLINE | ID: mdl-19218688

Ninety one patients with stroke or transient ischemic attack (TIA) were screened for sleep-disordered breathing (SDB). Case fatality, rate of recurrence of cerebrovascular events, and functional outcome were analyzed during a 2-year follow-up. The patients were stratified into groups: without (AH < or =5) and with SDB (AHI >5). SDB was present in 61 (67.7%) patients with stroke or TIA. The rate of recurrence of TIA or stroke in patients with SDB was significantly higher (12 patients, OR=1.52, P<0.05) as compared with patients without SDB (3 patients) within two years of observation. Case-fatality rates were not significantly different (4 patients with SDB and 2 patients without SDB). Our data show that SDB significantly increases the incidence of recurrent cerebrovascular events in patients with TIA or stroke in a two-year follow-up. SDB in patient with stroke or TIA did not influence functional outcome of stroke during the long-term observation.


Brain Ischemia/physiopathology , Cerebrovascular Disorders/mortality , Cerebrovascular Disorders/physiopathology , Ischemic Attack, Transient/physiopathology , Sleep Apnea Syndromes/mortality , Sleep Apnea Syndromes/physiopathology , Stroke/physiopathology , Aged , Brain Ischemia/complications , Brain Ischemia/mortality , Female , Humans , Ischemic Attack, Transient/complications , Ischemic Attack, Transient/mortality , Male , Middle Aged , Neurologic Examination , Poland/epidemiology , Recurrence , Stroke/etiology , Stroke/mortality , Treatment Outcome
20.
J Physiol Pharmacol ; 58 Suppl 5(Pt 2): 575-82, 2007 Nov.
Article En | MEDLINE | ID: mdl-18204171

Fifty five patients with ischemic stroke and 15 patients with transient ischemic attacks (TIA) were screened for sleep related breathing disorders (SRBD). Apnea-hypopnea index (AHI) and desaturation index (DI) were analyzed. The clinical status was assessed with National Institute of Health Stroke Scale (NIHSS). The patients with stroke were stratified into groups: without (AHI10). SRBD were present in 36 patients with stroke and in 10 patients with TIA. There were significant differences in the clinical status on admission, as quantified with NIHSS, between stroke patients with mild and moderate or severe SRBD. AHI positively correlated with NIHSS on admission in stroke patients (r=0.54, P<0.01). The final NIHSS score was significantly greater in patients with moderate or severe SRBD than in those with mild SRBD: 3.4+/-1.9 and 1.8+/-1.2, respectively. Our data suggest that the severity of SRBD is related to the clinical status on admission and it influence the clinical outcome after ischemic stroke.


Brain Ischemia/complications , Ischemic Attack, Transient/complications , Respiratory Mechanics/physiology , Sleep Apnea Syndromes/etiology , Sleep Apnea Syndromes/physiopathology , Stroke/complications , Stroke/etiology , Aged , Brain Ischemia/epidemiology , Female , Humans , Ischemic Attack, Transient/epidemiology , Male , Middle Aged , Poland/epidemiology , Risk Factors , Sleep Apnea Syndromes/epidemiology , Stroke/epidemiology , Treatment Outcome
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