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1.
Ann Med Surg (Lond) ; 85(9): 4570-4574, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37663747

ABSTRACT

Introduction and importance: Budd-Chiari Syndrome (BCS) is a rare disorder that affects the liver and is caused by blockage of the hepatic veins. Coronavirus disease 2019 (COVID-19) has been linked to an increased risk of developing BCS due to its ability to cause inflammation in the body, which can lead to clotting disorders. Case presentation: A 43-year-old female presented to the emergency department complaining of severe epigastric and right upper quadrant pain and progressive abdominal distention. Upon examination, investigation, and triphasic liver computed tomography with contrast, the patient was diagnosed with BCS. Clinical discussion: The patient was started on anticoagulant therapy with low-molecular-weight heparin and supportive treatment. She was hospitalized for 3 weeks and discharged on oral warfarin 5 mg/day after showing clinical improvement. Conclusion: Hepatosplenomegaly and abdominal distention after COVID-19 infection raise suspicion for BCS. Therefore, early detection of these signs is essential for immediate management.

2.
Cureus ; 14(11): e31407, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36514666

ABSTRACT

Transgender individuals experience lower overall health outcomes than cisgender individuals due to a higher burden of chronic illnesses in this demographic. An early loss in renal function is frequently seen in acute interstitial nephritis (AIN), which is defined by the presence of inflammatory infiltrates and edema inside the interstitium. Infections or medication use can cause interstitial nephritis. In two-thirds of cases, interstitial nephritis caused by drugs is detected. Few people are affected by it, thus, it's thought to be immune-mediated rather than dose-dependent. In this report, a 32-year-old transgender female was admitted to a hospital due to generalized swelling following filler injections in the buttocks region. It is important for doctors and patients to be informed about these procedures' potential risks. Additionally, more study has to be done on the negative effects of filler injections.

3.
Mol Ther Methods Clin Dev ; 26: 547-561, 2022 Sep 08.
Article in English | MEDLINE | ID: mdl-36092363

ABSTRACT

Huntington's disease (HD) is caused by an expanded CAG repeat in huntingtin (HTT). Since HD is dominant and loss of HTT leads to neurological abnormalities, safe therapeutic strategies require selective inactivation of mutant HTT. Previously, we proposed a concept of CRISPR-Cas9 using mutant-specific PAM sites generated by SNPs to selectively inactivate mutant HTT. Aiming at revealing suitable targets for clinical development, we analyzed the largest HD genotype dataset to identify target PAM-altering SNPs (PAS) and subsequently evaluated their allele specificities. The gRNAs based on the PAM sites generated by rs2857935, rs16843804, and rs16843836 showed high levels of allele specificity in patient-derived cells. Simultaneous use of two gRNAs based on rs2857935-rs16843804 or rs2857935-rs16843836 produced selective genomic deletions in mutant HTT and prevented the transcription of mutant HTT mRNA without impacting the expression of normal counterpart or re-integration of the excised fragment elsewhere in the genome. RNA-seq and off-target analysis confirmed high levels of allele specificity and the lack of recurrent off-targeting. Approximately 60% of HD subjects are eligible for mutant-specific CRISPR-Cas9 strategies of targeting one of these three PAS in conjunction with one non-allele-specific site, supporting high applicability of PAS-based allele-specific CRISPR approaches in the HD patient population.

4.
JCI Insight ; 7(19)2022 10 10.
Article in English | MEDLINE | ID: mdl-36040815

ABSTRACT

Dominant gain-of-function mechanisms in Huntington's disease (HD) suggest that selective silencing of mutant HTT produces robust therapeutic benefits. Here, capitalizing on exonic protospacer adjacent motif-altering (PAM-altering) SNP (PAS), we developed an allele-specific CRISPR/Cas9 strategy to permanently inactivate mutant HTT through nonsense-mediated decay (NMD). Comprehensive sequence/haplotype analysis identified SNP-generated NGG PAM sites on exons of common HTT haplotypes in HD subjects, revealing a clinically relevant PAS-based mutant-specific CRISPR/Cas9 strategy. Alternative allele of rs363099 (29th exon) eliminates the NGG PAM site on the most frequent normal HTT haplotype in HD, permitting mutant-specific CRISPR/Cas9 therapeutics in a predicted ~20% of HD subjects with European ancestry. Our rs363099-based CRISPR/Cas9 showed perfect allele specificity and good targeting efficiencies in patient-derived cells. Dramatically reduced mutant HTT mRNA and complete loss of mutant protein suggest that our allele-specific CRISPR/Cas9 strategy inactivates mutant HTT through NMD. In addition, GUIDE-Seq analysis and subsequent validation experiments support high levels of on-target gene specificity. Our data demonstrate a significant target population, complete mutant specificity, decent targeting efficiency in patient-derived cells, and minimal off-target effects on protein-coding genes, proving the concept of PAS-based allele-specific NMD-CRISPR/Cas9 and supporting its therapeutic potential in HD.


Subject(s)
Huntington Disease , Alleles , CRISPR-Cas Systems , Gain of Function Mutation , Humans , Huntingtin Protein/genetics , Huntingtin Protein/metabolism , Huntington Disease/genetics , Huntington Disease/therapy , Mutant Proteins/genetics , Mutant Proteins/metabolism , RNA, Messenger
5.
Mol Ther Methods Clin Dev ; 25: 84-95, 2022 Jun 09.
Article in English | MEDLINE | ID: mdl-35356757

ABSTRACT

Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by an expanded CAG repeat in huntingtin (HTT). Given an important role for HTT in development and significant neurodegeneration at the time of clinical manifestation in HD, early treatment of allele-specific drugs represents a promising strategy. The feasibility of an allele-specific antisense oligonucleotide (ASO) targeting single-nucleotide polymorphisms (SNPs) has been demonstrated in models of HD. Here, we constructed a map of haplotype-specific insertion-deletion variations (indels) to develop alternative mutant-HTT-specific strategies. We mapped indels annotated in the 1000 Genomes Project data on common HTT haplotypes, revealing candidate indels for mutant-specific HTT targeting. Subsequent sequencing of an HD family confirmed candidate sites and revealed additional allele-specific indels. Interestingly, the most common normal HTT haplotype carries indels of big allele length differences at many sites, further uncovering promising haplotype-specific targets. When patient-derived cells carrying the most common HTT diplotype were treated with ASOs targeting the mutant alleles of candidate indels (rs772629195 or rs72239206), complete mutant specificity was observed. In summary, our map of haplotype-specific indels permits the identification of allele-specific targets in HD subjects, potentially contributing to the development of safe HTT-lowering therapeutics that are suitable for early treatment in HD.

6.
Epilepsy Behav ; 124: 108332, 2021 Oct 04.
Article in English | MEDLINE | ID: mdl-34619544

ABSTRACT

OBJECTIVE: Red-light filtering lenses represent an additional option to medication in photosensitive epilepsy. Blue lenses (Clarlet Z1 F133) can dramatically reduce seizure frequency, with a substantial restriction in luminance that can limit their applicability in daily life. We investigated the efficacy of 4 blue lenses with higher transmittance and reduced chromatic distortion in abolishing the photoparoxysmal EEG response (PPR) compared to the gold-standard Z1 lenses. METHODS: We reviewed EEG data during photic-and pattern stimulation in 19 consecutive patients (6-39 years) with photosensitivity (PS). Stimulation was performed at baseline and while wearing Z1 and the four new lenses. Lenses were tested in the same session by asking the patient to wear them in a sequentially randomized fashion while stimulating again with the most provocative photic/pattern stimuli. The primary outcome was the change in the initial PPR observed for each lens, categorized as no change, reduction, and abolition. RESULTS: Photosensitivity was detected in 17 subjects (89.5%); pattern sensitivity (PtS) was identified in 14 patients (73.7%). The highest percentages of PPR abolition/reduction were observed with Z1, for both PS and PtS. Regarding the new lenses, B1 + G1 offered the best rates, followed by B1 + G2. B1 + G3 and B1 showed lower efficacy rates, particularly for PtS. In the comparative analysis, no significant differences in PPR suppression were detected between the five lenses for PS. For PtS, the capacity of Z1 for PPR abolition was significantly higher compared with B1 + G3 and B1. CONCLUSIONS: This preliminary study suggests efficacy of the new group of blue lenses with potentially greater tolerability, particularly in regions with fewer sunlight hours during winter. In line with the current trend for personalized approach to treatment, this study suggests that in some patients there might be scope in extending the testing to offer the lens with the higher transmittance effective in abolishing the PPR.

7.
Neuroimage Clin ; 23: 101844, 2019.
Article in English | MEDLINE | ID: mdl-31075554

ABSTRACT

Paediatric traumatic brain injury (pTBI) is a leading cause of disability for children and young adults. Children are a uniquely vulnerable group with the disease process that occurs following a pTBI interacting with the trajectory of normal brain development. Quantitative MRI post-injury has suggested a long-term, neurodegenerative effect of TBI on the morphometry of the brain, in both adult and childhood TBI. Changes to the brain beyond that of anticipated, age-dependant differences may allow us to estimate the state of the brain post-injury and produce clinically relevant predictions for long-term outcome. The current review synthesises the existing literature to assess whether, following pTBI, the morphology of the brain exhibits either i) longitudinal change and/or ii) differences compared to healthy controls and outcomes. The current literature suggests that morphometric differences from controls are apparent cross-sectionally at both acute and late-chronic timepoints post-injury, thus suggesting a non-transient effect of injury. Developmental trajectories of morphometry are altered in TBI groups compared to patients, and it is unlikely that typical maturation overcomes damage post-injury, or even 'catches up' with that of typically-developing peers. However, there is limited evidence for diverted developmental trajectories being associated with cognitive impairment post-injury. The current review also highlights the apparent challenges to the existing literature and potential methods by which these can be addressed.


Subject(s)
Brain Injuries, Traumatic/diagnostic imaging , Brain/diagnostic imaging , Magnetic Resonance Imaging/trends , Brain/physiopathology , Brain Injuries, Traumatic/physiopathology , Child , Cross-Sectional Studies , Humans , Longitudinal Studies , Magnetic Resonance Imaging/methods
8.
JBI Database System Rev Implement Rep ; 15(4): 1209-1219, 2017 04.
Article in English | MEDLINE | ID: mdl-28398988

ABSTRACT

BACKGROUND: Patients with cancer are often at risk or suffer from some form of malnutrition, which could be attributed to their disease progression or the adverse effects of cancer treatment. Protected mealtime and offering assistance during mealtime may not improve their nutritional status but would allow them to enjoy their meal and improve patient satisfaction. OBJECTIVES: The aim of this project was to promote best practice in protecting mealtimes in hematology-oncology patients. METHODS: The current project adopted a clinical audit methodology using the Joanna Briggs Institute Practical Application of Clinical Evidence System tool. Four audit criteria that represent best practice recommendations for protected mealtimes were used. A pre-implementation audit was conducted followed by introduction of multiple interventions identified from the Getting Research into Practice analysis. A post implementation audit was conducted to determine the change of practice. In addition, a sustaining audit was conducted at six months after implementing the follow-up plan. RESULTS: The four criteria showed an improvement: nurses ensured a pleasant eating environment around the patient cubicle (from 43% to 93% compliance), all nurses received education on mealtime care (no change - 100% sustenance), nurses conducted an assessment of the patients on admission on their ability to eat (from 95% to 100% compliance) and minimized unnecessary clinical interventions during mealtimes (92% to 89% compliance). The decline of 3% in the compliance rate of the last criterion could be attributed to the high turnover of patients during the post implementation audit period. The post implementation results at six months showed audit results being sustained at 100% compliance in all criteria. CONCLUSION: The results of this project demonstrated that improvement in best practice is possible in a busy oncology ward in the presence of great leadership, teamwork, empowerment and role modeling.


Subject(s)
Hematology , Meals/psychology , Medical Oncology , Neoplasms/therapy , Adult , Hospitals , Humans , Malnutrition/prevention & control , Neoplasms/psychology , Practice Guidelines as Topic
9.
J Neural Eng ; 14(1): 011001, 2017 02.
Article in English | MEDLINE | ID: mdl-28068295

ABSTRACT

Support vector machines (SVMs) are widely used classifiers for detecting physiological patterns in human-computer interaction (HCI). Their success is due to their versatility, robustness and large availability of free dedicated toolboxes. Frequently in the literature, insufficient details about the SVM implementation and/or parameters selection are reported, making it impossible to reproduce study analysis and results. In order to perform an optimized classification and report a proper description of the results, it is necessary to have a comprehensive critical overview of the applications of SVM. The aim of this paper is to provide a review of the usage of SVM in the determination of brain and muscle patterns for HCI, by focusing on electroencephalography (EEG) and electromyography (EMG) techniques. In particular, an overview of the basic principles of SVM theory is outlined, together with a description of several relevant literature implementations. Furthermore, details concerning reviewed papers are listed in tables and statistics of SVM use in the literature are presented. Suitability of SVM for HCI is discussed and critical comparisons with other classifiers are reported.


Subject(s)
Brain-Computer Interfaces , Electroencephalography/methods , Electromyography/methods , Man-Machine Systems , Pattern Recognition, Automated/methods , Support Vector Machine , Algorithms , Brain/physiology , Evoked Potentials/physiology , Humans , Muscle Contraction/physiology , Muscle, Skeletal/physiology , Robotics/methods
10.
Clin Neurophysiol ; 122(1): 16-20, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20591728

ABSTRACT

OBJECTIVE: To investigate visual habituation - a measure of visual cortical excitability - in photosensitive patients in pediatric age and compare the findings with a matched sample with idiopathic generalized epilepsies without photosensitivity and with normally developing children. METHODS: We presented a full-field black-and-white checkerboard pattern, at 3 reversal/s with 100% contrast binocularly for 600 consecutive trials and measured the N75-P100 and P100-N145 pattern-reversal visual evoked potential inter-peak amplitudes and N75, P100, N145 latencies for the six blocks of 100 responses. As a measure of habituation we used the slope of the linear regression line of the N75-P100 and P100-N145 peak-to-peak amplitudes. The slope of the linear regression line of the N75-P100 and P100-N145 latencies was also analyzed. RESULTS: Statistical analysis revealed significant differences between the three groups in the slope index of N75-P100 PR-VEP amplitude, with increased or constant amplitude in the PS group compare to the IGE and ND across the six blocks. CONCLUSIONS: Our results support the notion that photosensitivity is associated with altered control of excitatory and inhibitory cortical processes. The causal relationship between habituation deficit and photo-paroxysmal response needs to be further investigated with longitudinal studies. SIGNIFICANCE: This study supports the hypothesis that suppression of PR-VEP is a sensitive intermediate phenotype, which discriminates patients with photosensitivity from those with generalized epilepsies in pediatric age.


Subject(s)
Epilepsy, Reflex/diagnosis , Epilepsy, Reflex/physiopathology , Habituation, Psychophysiologic/physiology , Visual Cortex/physiopathology , Visual Perception/physiology , Adolescent , Brain Waves/physiology , Child , Electroencephalography/methods , Female , Humans , Male , Photic Stimulation/methods
11.
J Obstet Gynaecol Res ; 37(2): 132-7, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21159037

ABSTRACT

AIM: To evaluate the safety and tolerability of once or twice daily neutral protamine hagedorn (NPH) insulin in fasting pregnant diabetics during Ramadan. METHODS: This was a prospective cohort study conducted during Ramadan 2006 and 2007. Twenty four pregnant diabetic women were given NPH insulin once at 5 pm or twice daily at 5 pm and 5 am. Demographic data, blood glucose control, insulin requirement, days of fasting and hypoglycemic episodes were analyzed. RESULTS: Most women were parity 1 (37.5%) in their second trimester (54.2%) and worked during the daytime (87.5%). Fourteen women (58.3%) had gestational diabetes mellitus, nine women (37.5%) had type 2 and one (4.2%) had type 1 diabetes mellitus. There were significant reductions in mean fasting blood glucose (6.16 mmol/L versus 5.34 mmol/L, P = 0.001), glycosylated hemoglobin (HbA1c) (6.70% ± 0.91 versus 6.64% ± 0.96, P = 0.001) and serum fructosamine (232.4 mmol/L ± 24.0 versus 217.0 mmol/L ± 24.3, P = 0.001) after Ramadan compared to before Ramadan. Throughout the four weeks of Ramadan, home blood glucose monitoring showed a reducing trend and was within the acceptable limits. Insulin requirement was increased from the first to the fourth week with a reduction in insulin dose noted after (38.5 U/day) compared to before the start of Ramadan (40 U/day). Most women (79.2%) were able to fast for more than 15 days without any hypoglycemia or fetal demise. CONCLUSION: Once or twice daily NPH insulin is a safe and tolerable option for pregnant diabetics who wish to fast during Ramadan.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Diabetes, Gestational/drug therapy , Fasting , Insulin, Isophane/therapeutic use , Islam , Pregnancy in Diabetics/drug therapy , Adult , Blood Glucose/analysis , Blood Glucose Self-Monitoring , Cohort Studies , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Diabetes, Gestational/blood , Drug Administration Schedule , Female , Humans , Insulin, Isophane/administration & dosage , Parity , Pregnancy , Pregnancy in Diabetics/blood , Prospective Studies , Treatment Outcome
13.
Asia Pac J Clin Nutr ; 15(3): 388-99, 2006.
Article in English | MEDLINE | ID: mdl-16837432

ABSTRACT

The objective of the study was to assess nutritional and health status as well as nutritional knowledge in urban middle-aged Malaysian women. The impact of menopause on diet and health indices was also studied. The study included 360 disease free women, non users of HRT,aged > or =45 years with an intact uterus recruited from November 1999 to October 2001. Personal characteristics, anthropometric measurements and blood sample were acquired followed by clinical examination. Nutrient intake and nutritional knowledge was determined by a quantitative FFQ and KAP. The findings showed that urban middle-aged women, aged 51.65+/-5.40 years had energy intakes (EI) 11% below RDA, consisting of 53% carbohydrates, 15% protein and a 32% fat which declined with age. The sample which comprised of 42.5% postmenopausal women had a satisfactory diet and healthy lifestyle practices. Premenopausal women consumed more dietary fat (6%) with other aspects of diet comparable to the postmenopausal women. Iron intake was deficient in premenopausal women, amounting to 56% RDA contributing to a 26% prevalence of anaemia. Overall, calcium intake reached 440 mg daily but dairy products were not the main source. The postmenopaused had a more artherogenic lipid profile with significantly higher total cholesterol (TC) and LDL-C, but more premenopausal women were overweight/obese (49% versus 35%). EI was the strongest predictor for BMI and waist circumference (WC), with WC itself an independent predictor of fasting blood sugar and TC with BMI strongly affecting glucose tolerance. High nutritional knowledge was seen in 39% whereas 20% had poor knowledge. Newspapers and magazines, followed by the subject's social circle, were the main sources of nutritional information. Nutritional knowledge was positively associated with education, household income, vitamin/ mineral supplementation and regular physical activity but inversely related to TC. In conclusion, middle-aged urban women had an adequate diet with low iron and calcium intakes. Nutritional knowledge was positively associated to healthier lifestyle practices and lower TC. A comparable nutrient intake and lifestyle between pre and postmenopausal women suggested that health changes associated with menopause was largely independent of diet.


Subject(s)
Diet , Health Knowledge, Attitudes, Practice , Health Status , Nutritional Physiological Phenomena , Anthropometry , Body Mass Index , Calcium, Dietary/administration & dosage , Dietary Carbohydrates/administration & dosage , Dietary Fats/administration & dosage , Dietary Proteins/administration & dosage , Energy Intake , Female , Humans , Lipids/blood , Malaysia , Menopause , Middle Aged , Nutrition Policy , Postmenopause
14.
Osteoporos Int ; 16(12): 2069-79, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16234999

ABSTRACT

The aim of this study was to identify risk factors associated with osteoporosis in urban midlife Malaysian women and to assess the effectiveness of lifestyle intervention in bone loss prevention with hormone replacement therapy (HRT) as a positive control. A total of 514 disease-free, uterus-intact, non-HRT-using women aged 45 years and older were recruited into the study. After initial bone mineral density (BMD) assessments, they were randomized into three groups: GI (control), G2 (lifestyle intervention), and G3 (lifestyle intervention with HRT). The study group was composed of 67.5% Chinese, 27.8% Malay, and 4.2% Indians with a mean age of 51.07+/-5.28 years. Two-fifths were postmenopausal, and the prevalence of osteoporosis was 24.1%, seen predominantly at the hip. Postmenopausal women had significantly lower mean BMD and a higher incidence of osteoporosis compared with the premenopausal women, 42.1% vs. 11.1% (p<0.0005). A lower incidence of osteoporosis was found in women who took calcium supplementation regularly as opposed to those who do not, 18.7% vs. 29.3% (p=0.036). Age and a greater postmenopausal duration showed a significant negative association with BMD, whereas higher family income, weight, body mass index, and waist and hip circumference were positively correlated. After 18-20 months, the effect of intervention was assessed based on BMD values of 279 women at baseline and after intervention. Lifestyle intervention alone was effective in premenopausal women, preventing over 90% of spinal bone loss compared with the controls, who lost 11.6% (0.046 g/cm2) bone mass with similar losses of hip bone, 2.0% (0.026 g/cm2) vs. 1.5% (0.020 g/cm2). Premenopausal women on HRT also showed a substantial decrease in spine and hip BMD, 18.6% (0.081 g/cm2) and 9.0% (0.122 g/cm2), respectively. The lifestyle intervention program retarded postmenopausal bone loss by 21% and 37% compared with controls, who lost 9.6% (0.141 g/cm2) and 6.0% (0.138 g/cm2) bone mass at the spine and hip. In comparison, lifestyle intervention with HRT increased postmenopausal BMD by 12.7% (0.216 g/cm2) at the spine and 1.9% (0.042 g/cm2) at the hip. The changes in hip BMD were influenced by current age, ethnicity, and income, while intervention had the strongest effect on spine BMD changes. In conclusion, lifestyle intervention prevented spinal bone loss in premenopausal women and retarded postmenopausal spine and hip bone loss compared with controls. The benefits of physical activity on spine and hip BMD highlight its potential as a safe and cost-effective alternative to HRT, which is not advocated because of its potential adverse effects.


Subject(s)
Osteoporosis/prevention & control , Adult , Age Distribution , Body Size , Bone Density/physiology , Calcium, Dietary/administration & dosage , Dietary Supplements , Female , Hip , Hormone Replacement Therapy/methods , Humans , Incidence , Life Style , Malaysia/epidemiology , Middle Aged , Osteoporosis/epidemiology , Osteoporosis/ethnology , Osteoporosis, Postmenopausal/epidemiology , Osteoporosis, Postmenopausal/ethnology , Osteoporosis, Postmenopausal/prevention & control , Perimenopause/physiology , Risk Factors , Spine , Treatment Outcome , Urban Health
15.
Int J Cardiovasc Imaging ; 21(5): 539-47, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16175444

ABSTRACT

PURPOSE: Our objective was to evaluate the use of a new medium weight MRI contrast agent, NMS60 (a synthetic oligomeric Gd-complex containing three Gd(3+) atoms, molecular weight 2158 Da) compared to gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) in a pig myocardial ischemia model. MATERIALS: We used 13 male white hybrid pigs. Animals were scanned in the acute phase 2-3 h after the onset of myocardial ischemia. Scans were acquired on a 1.5T GE Signa with dynamic T1-weighted imaging during a bolus injection of 0.1 mmol(gd)/kg of either NMS60 or Gd-DTPA, 2D CINE at 5 min after injection, and T1-weighted spin-echo imaging up to 60 min. RESULTS: The postcontrast CINE scans showed improved contrast-to-noise ratio after NMS60 injection, compared to Gd-DTPA. There was significantly greater enhancement with NMS60 in both normal myocardium and in the ischemic lesion on T1-weighted spin-echo scans up to 60 min after injection. The dose ranging study shows a 24% greater enhancement with NMS60 compared to Gd-DTPA. DISCUSSION: This new medium weighted contrast agent offers improved enhancement for cardiac MRI, compared to Gd-DTPA, with similar washout kinetics and lower toxicity, and may prove useful for better detection of myocardial ischemia as well as delayed or hyperenhancement after reperfusion.


Subject(s)
Contrast Media , Gadolinium DTPA , Magnetic Resonance Imaging, Cine , Myocardial Ischemia/pathology , Organometallic Compounds , Acute Disease , Animals , Disease Models, Animal , Image Processing, Computer-Assisted , Male , Swine
16.
J Magn Reson Imaging ; 22(4): 461-6, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16142700

ABSTRACT

PURPOSE: To study a new gadolinium (Gd) contrast agent-NMS60-for MR perfusion-weighted imaging (PWI) of brain tissue. MATERIALS AND METHODS: NMS60 is a Gd3+ trimer with a molecular weight of 2158 Daltons, and a T2 relaxivity almost three times higher than that of Gd-DTPA. Middle cerebral artery (MCA) occlusion was induced in nine nonhuman primates. The animals were scanned acutely and for up to six follow-up time points. PWI peak, and time-to-peak maps were generated, and perfusion deficit volumes were measured from these maps. The values of peak, time-to-peak, and perfusion deficit volume were compared between NMS60 and GD-DTPA. RESULTS: These results demonstrate that there was no significant difference in our calculated perfusion parameters between the two contrast agents. CONCLUSION: The two agents were found to be equally effective for PWI for acute and chronic stroke in primates. Along with its previously demonstrated advantage for T1-enhanced imaging, the current results show that NMS60 is a viable contrast agent for use in stroke patients.


Subject(s)
Brain Ischemia/diagnosis , Contrast Media , Gadolinium DTPA , Magnetic Resonance Angiography/methods , Organometallic Compounds , Animals , Infarction, Middle Cerebral Artery/diagnosis , Macaca , Male
17.
Neurology ; 63(10): 1968-70, 2004 Nov 23.
Article in English | MEDLINE | ID: mdl-15557528

ABSTRACT

The authors report the unusual clinical and neurophysiologic features of a sporadic case of a boy carrying an 806delG mutation on the MECP2 gene. A 28-month-old boy was examined for severe developmental delay, seizures, microcephaly, breathing dysfunction, and spontaneous and evoked myoclonic jerks of upper limbs. Neurophysiologic study proved the cortical origin of myoclonus; however, it was not associated with signs of cortical hyperexcitability. 3-Methoxy-4-hydroxy-phenylethylene glycol and valine concentrations were low in CSF.


Subject(s)
Chromosomal Proteins, Non-Histone/genetics , DNA-Binding Proteins/genetics , Developmental Disabilities/genetics , Epilepsies, Partial/genetics , Epilepsy, Tonic-Clonic/genetics , Genetic Diseases, X-Linked/genetics , Myoclonic Epilepsy, Juvenile/genetics , Repressor Proteins/genetics , Chromosomal Proteins, Non-Histone/deficiency , Codon, Nonsense , DNA Mutational Analysis , DNA-Binding Proteins/deficiency , Developmental Disabilities/cerebrospinal fluid , Developmental Disabilities/physiopathology , Electroencephalography , Electromyography , Epilepsy, Tonic-Clonic/cerebrospinal fluid , Epilepsy, Tonic-Clonic/physiopathology , Evoked Potentials, Somatosensory , Genetic Diseases, X-Linked/cerebrospinal fluid , Genetic Diseases, X-Linked/classification , Genetic Diseases, X-Linked/diagnosis , Genetic Diseases, X-Linked/physiopathology , Humans , Infant, Newborn , Magnetic Resonance Imaging , Male , Methoxyhydroxyphenylglycol/cerebrospinal fluid , Methyl-CpG-Binding Protein 2 , Microcephaly/genetics , Myoclonic Epilepsy, Juvenile/cerebrospinal fluid , Myoclonic Epilepsy, Juvenile/physiopathology , Psychomotor Disorders/cerebrospinal fluid , Psychomotor Disorders/genetics , Psychomotor Disorders/physiopathology , Respiration Disorders/genetics , Rett Syndrome/genetics , Sequence Deletion , Sex Factors , Status Epilepticus/etiology , Video Recording
18.
Magn Reson Imaging ; 22(5): 619-24, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15172054

ABSTRACT

In a canine model the signal dynamics of a new oligomer-based MR contrast agent (NMS60, 2158 Da) were compared to Gd-DTPA to investigate the agents' potential for magnetic resonance angiography (MRA). Twelve male mongrel dogs were imaged sequentially under anesthesia with two different MRA sequences (Tlw 3DSPGR). Initial enhancement was measured every 9 s for eight points in time. Thereafter, spatial highly resolved MRAs were obtained at 5, 10, 15, 20, 30, 45, and 60 min post-injection of two different dosages. Over the first 20 s following bolus administration the average arterial enhancement of 0.1 mmol(Gd)kg NMS60 was 44% greater than Gd-DTPA. Twenty minutes post-injection the relative signal intensity of NMS60 was as high as the peak signal intensity with Gd-DTPA at the same dosage level (0.1 mmol(Gd)/kg). In the animals that received NMS60 injections the vascular conspicuity was overly superior to those who received Gd-DTPA. No significant toxicity effects were noted for either dosage level. The intermediate weight contrast agent NMS60 offers greater vascular enhancement and retention time than Gd-DTPA. For a given set of optimized imaging parameters this offers improved spatial details, less arterial/venous overlap, and better vascular contrast.


Subject(s)
Contrast Media , Gadolinium DTPA , Organometallic Compounds , Animals , Contrast Media/chemistry , Contrast Media/toxicity , Dogs , Gadolinium DTPA/chemistry , Gadolinium DTPA/toxicity , Lethal Dose 50 , Magnetic Resonance Angiography , Male , Organometallic Compounds/chemistry , Organometallic Compounds/toxicity , Rats
19.
Pediatr Neurosurg ; 37(5): 225-30, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12411712

ABSTRACT

AIM: Investigation of the effect of intrathecal baclofen administration on the time course of electrical patterns of muscle activation in patients with spasticity due to upper motor neuron syndrome. METHODS: Six children with clinical signs of upper motor neuron syndrome resulting from an acquired cerebral hypoxic injury were tested. Simultaneous multichannel acquisition of surface EMG activity from flexor/extensor muscle groups of the upper and lower limbs was recorded. Investigated muscle group pairs included biceps/triceps brachii, wrist flexors/extensors, rectus/biceps femoris and tibialis anterioris/gastrocnemius. Time-frequency analysis of EMG activity at rest and while eliciting a stretch reflex was performed. The non-linear cross-correlation coefficient and time lag estimation were computed between paired channel groups both for baseline and post-intrathecal baclofen injection conditions for epochs consisting of 2 s prior to and 2 s after voluntary contraction. The effect of baclofen was assessed 3 h following single-bolus intrathecal injections of 25 or 50 microg during the baclofen trial and 6 months after baclofen pump implantation. RESULTS: In the baseline condition, the stretch reflex resulted in a synchronous increase in spectral EMG power in both the agonist and the antagonist muscles. The mean correlation coefficient between agonist and antagonist muscles was 0.948 (SD = 0.034), and the mean time lag was 4.64 ms (SD = 1.84 ms). After intrathecal administration of baclofen, a dramatic decrease in the correlation coefficient between agonist and antagonists (mean value = 0.342) during voluntary contraction was observed. This corresponded to a significant reduction of tone and spasticity in all four limbs, and reduction of the Ashworth score by 2 points on average. CONCLUSION: After intrathecal baclofen administration, we observed a significant decrease in the co-contraction pattern typically associated with upper motor neuron spasticity. This was evident clinically and was quantitatively expressed by the significantly decreased degree of coupling in EMG activity of agonist/antagonist muscles. Although a relatively small sample was investigated in this study, we were able to demonstrate the efficacy of this procedure in restoring selective activation of agonists during voluntary contraction. This is one of the prerequisites of an improvement of motor function in patients with spasticity.


Subject(s)
Baclofen/pharmacology , Baclofen/therapeutic use , Cerebral Palsy/complications , Cerebral Palsy/drug therapy , Motor Neuron Disease/complications , Motor Neuron Disease/drug therapy , Muscle Contraction/drug effects , Muscle Relaxants, Central/pharmacology , Muscle Relaxants, Central/therapeutic use , Muscle Spasticity/drug therapy , Muscle Spasticity/etiology , Adolescent , Baclofen/administration & dosage , Cerebral Palsy/physiopathology , Child , Electromyography , Female , Follow-Up Studies , Humans , Injections, Spinal , Male , Motor Neuron Disease/physiopathology , Muscle Contraction/physiology , Muscle Relaxants, Central/administration & dosage , Muscle Spasticity/physiopathology , Muscle, Skeletal/drug effects , Muscle, Skeletal/physiopathology , Time Factors
20.
Dev Med Child Neurol ; 43(11): 735-8, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11730146

ABSTRACT

The study aimed to determine if melatonin could reliably induce sleep in children undergoing sleep EEG without affecting the usefulness of the EEG itself. One hundred and sixty three children (112 males, 51 females; mean age 8 years, range 1 to 16 years) referred for sleep EEG were studied. The children were given 2 to 10 mg of melatonin, depending on age, just before EEG recording. Measurements included sleep-onset latency, adverse effects, and acceptability of the EEG. Usefulness and acceptability of melatonin-induced sleep EEG were compared with the standard technique of sleep EEG following sleep deprivation in 30 children (matched for sex and age). Sleep was obtained in 79% of the 163 children who received melatonin after an average of 33 minutes. Yield of epileptiform abnormalities demonstrated in the melatonin sleep EEG was similar to that reported in the literature for sleep-deprived EEGs. There was no significant adverse effect. When compared, a melatonin-induced sleep EEG was as useful as a sleep-deprived EEG. However, the children's behaviour on the day of the melatonin-induced sleep EEG recording was more acceptable to parents.


Subject(s)
Antioxidants/pharmacology , Electroencephalography , Melatonin/pharmacology , Sleep/drug effects , Antioxidants/therapeutic use , Child , Child, Preschool , Female , Humans , Male , Melatonin/therapeutic use , Sleep Deprivation/drug therapy , Surveys and Questionnaires , Time Factors , Treatment Outcome
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