PubMed Health⌕ Search

Biomedical subjects

J Sharp

Publications and source records attributed to J Sharp.

At least 19 recordsLinked to original sources
PubMed2001

The engineering of an interventional MRI with a movable 1.5 Tesla magnet.

The engineering of a novel intra-operative MRI system is described. A movable, 1.5 Tesla MRI magnet was placed in a neurosurgical operating room without affecting established neurosurgical procedure. The system allows fast, high-quality MR intra-operative imaging of the brain and spine without the necessity of patient transportation. A neuro-navigational device capable of displaying and updating spatially referenced MR images in the operating room was integrated with the MRI system. Over 100 procedures have been carried out with this system without limiting surgical access and without compromising traditional neurosurgical, nursing or anesthetic techniques. J. Magn. Reson. Imaging 2001;13:78-86.

Brain↗
PubMed2001

Two-year, blinded, randomized, controlled trial of treatment of active rheumatoid arthritis with leflunomide compared with methotrexate. Utilization of Leflunomide in the Treatment of Rheumatoid Arthritis Trial Investigator Group.

OBJECTIVE: Three 6-12-month, double-blind, randomized, controlled trials have shown leflunomide (LEF; 20 mg/day, loading dose 100 mg x 3 days) to be effective and safe for the treatment of rheumatoid arthritis (RA). This analysis of the North American trial assessed whether the clinical benefit evident at month 12 was sustained over 24 months of treatment with LEF as compared with the efficacy and safety of methotrexate (MTX), an equivalent disease-modifying antirheumatic drug, at 24 months. METHODS: The year-2 cohort, comprising patients continuing into the second year of treatment with > or = 1 dose of study medication and > or = 1 followup visit after week 52, consisted of 235 patients (LEF n = 98; placebo n = 36; MTX n = 101). The mean (+/- SD) maintenance dose of LEF was 19.6 +/- 1.99 mg/day in year 2 and that of MTX was 12.6 +/- 4.69 mg/week. Statistical analyses used an intent-to-treat (ITT) approach. Statistical comparisons of the active treatments only were prospectively defined in the protocol. RESULTS: In total, 85% and 79% of LEF and MTX patients, respectively, who entered year 2 completed 24 months of treatment. From month 12 to month 24, the American College of Rheumatology improvement response rates of > or = 20% (LEF 79% versus MTX 67%; P = 0.049), > or = 50% (LEF 56% versus MTX 43%; P = 0.053), and > or = 70% (LEF 26% versus MTX 20%; P = 0.361) were sustained in both of the active treatment groups. The mean change in total Sharp radiologic damage scores at year 2 compared with year 1 and baseline (LEF 1.6 versus MTX 1.2) showed statistically equivalent sustained retardation of radiographic progression in the active treatment groups. Maximal improvements evident at 6 months in the Health Assessment Questionnaire (HAQ) disability index (HAQ DI) and the physical component score of the Medical Outcomes Survey 36-item short form were sustained over 12 months and 24 months; improvement in the HAQ DI with LEF4(-0.60) was statistically significantly superior to that with MTX (-0.37) at 24 months (P = 0.005). Over 24 months in the ITT cohort, serious treatment-related adverse events were reported in 1.6% of the LEF-treated patients and 3.7% of the MTX-treated patients. Frequently reported adverse events included upper respiratory tract infections, diarrhea, nausea and vomiting, rash, reversible alopecia, and transient liver enzyme elevations. CONCLUSION: The safety and efficacy of LEF and MTX were maintained over the second year of this 2-year trial. Both active treatments retarded radiographic progression over 24 months. LEF was statistically significantly superior to MTX in improving physical function as measured by the HAQ DI over 24 months of treatment. Results indicate that LEF is a safe and effective initial treatment for active RA, with clinical benefit sustained over 2 years of treatment without evidence of new or increased toxicity.

Adult↗
PubMed2001

Haemodialysing infants: theoretical limitations, and single versus double lumen lines.

Haemodialysing small infants is difficult because of vascular access limitations. We show that Poiseuille's law (that flow through a tube varies with its radius4) makes it inevitable that the blood flow that can be achieved in smaller patients will fall disproportionately compared to their need for dialysis. Poiseuille's law also predicts that for single and multiple lumen cannulae of the same outside gauge, blood flow through the single lumen will be several times greater. Measurements confirmed this. It is argued that haemodialysis efficiency will therefore be improved by using a single lumen cannula to alternately withdraw and return blood, compared to sampling and returning continuously through a multiple lumen cannula, despite only withdrawing for half the time.

Catheterization↗
PubMed2001

Attention deficit hyperactivity disorder (ADHD) and the dopamine D4 receptor gene: evidence of association but no linkage in a UK sample.

Recent studies report association and linkage between attention deficit hyperactivity disorder (ADHD) and the 7-repeat allele of a 48 base-pair repeat in the dopamine D4 receptor gene (DRD4). We examined the frequency of this allele in a sample of probands with DSM-IV ADHD using a case-control design, as well as the transmission disequilibrium test (TDT) and haplotype-based haplotype relative risk (HHRR) in the subset of probands with DNA available from both parents. One hundred and thirty-two ADHD probands were compared with 189 controls (chi(2) = 6.17, 1 df, P = 0.01, OR = 1.73, 95% CI = 1.11--2.71). A total of 85 complete trios were available for within-family tests of association and linkage. Fifty-two heterozygous parents carrying one copy of the 7-repeat were informative for the TDT (29 transmitted vs 23 non-transmitted, chi(2) = 0.69). Analysis of the entire sample of 132 probands using TRANSMIT provided no additional evidence for excess transmission of the 7-repeat allele (58 transmitted vs 54 non-transmitted). HHRR gave similar results. We conclude that the case-control findings are likely to be falsely positive, resulting from genetic stratification. However we can not rule out alternative explanations of low statistical power and gene-environment correlation.

Alleles↗
PubMed2001

Association study of a dopamine transporter polymorphism and attention deficit hyperactivity disorder in UK and Turkish samples.

Molecular genetic studies in attention deficit hyperactivity disorder (ADHD) have focussed on candidate genes within the dopamine system, which is thought to be the main site of action of stimulant drugs, the primary pharmacological treatment of the disorder. Of particular interest are findings with the dopamine transporter gene (DAT1), since stimulant drugs interact directly with the transporter protein. To date, there have been eight published association studies of ADHD with a 480 base-pair allele of a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of the gene, five that support an association and three against. We have analysed the same VNTR marker in a dataset of UK Caucasian children and an independent dataset of Turkish Caucasian children with DSM-IV ADHD, using the transmission disequilibrium test (TDT). Results from the UK (chi(2) = 8.97, P = 0.001, OR = 1.95), but not the Turkish sample (chi(2) = 0.93, P = 0.34) support association and linkage between genetic variation at the DAT1 locus and ADHD. When considered alongside evidence from other published reports, there is only modest evidence for the association, consistent with a very small main effect for the 480-bp allele (chi(2) = 3.45, P = 0.06, OR = 1.15), however we find significant evidence of heterogeneity between the combined dataset (chi(2) = 22.64, df = 8, P = 0.004).

3' Untranslated Regions↗
PubMed2000

Oral health in children with renal disease.

Thirty-eight children (aged 2-16 years) attending a regional kidney unit had a full clinical and radiological dental examination. Twenty had previously undergone a renal transplant, 11 had chronic renal failure and 7 had other renal diseases. Periodontal disease was uncommon The presence of gingival hyperplasia (gum overgrowth), as recorded in 22 of the children, did not show any relationship with the use of immunosuppressant therapy. However, gingival overgrowth was so excessive in 2 patients that surgical removal was required. The prevalence of dental caries was low. Enamel defects were common, and of an unusual pattern, with a much higher prevalence of diffuse opacities and enamel hypoplasia than in the normal child population, 83% and 22%, respectively. This increased prevalence is probably due to disordered calcium and phosphate metabolism. The prevalence of these defects may reflect an early onset of renal disease, since there were a number of very young children in the programme. Dental and medical care should be closely integrated for children with renal disease to avoid the undesirable dental sequelae of, in particular, gingival overgrowth, carcinoma and enamel hypoplasia.

Adolescent↗
PubMed1999

Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group.

CONTEXT: Leflunomide is a reversible inhibitor of de novo pyrimidine synthesis shown to be effective in a phase 2 trial in 402 patients with active rheumatoid arthritis (RA). OBJECTIVE: To compare the efficacy and safety of leflunomide treatment with placebo and methotrexate treatment in patients with active RA. DESIGN: Randomized, double-blind, placebo, and active-controlled 12-month study. SETTING: Forty-seven university and private rheumatology practices in the United States and Canada. PATIENTS: Diagnosis of RA by the American College of Rheumatology (ACR) criteria for duration of 6 months or longer and no previous methotrexate treatment. INTERVENTION: Leflunomide treatment (20 mg/d), placebo, or methotrexate treatment (7.5-15 mg/wk). MAIN OUTCOME MEASURES: American College of Rheumatology success rate (completed 52 weeks of treatment and met the ACR > or = 20% response criteria), disease progression as assessed by x-ray films, and improvement in function and health-related quality of life using the intent-to-treat population. RESULTS: The 482 patients studied were predominantly women (mean age, 54 years; mean disease duration, 6.7 years) for whom a mean of 0.8 disease-modifying antirheumatic drugs had failed. The ACR response and success rates for patients receiving leflunomide treatment (52% and 41%, respectively) and methotrexate treatment (46% and 35%, respectively) were significantly higher than those for patients receiving placebo (26% and 19%, respectively) (P<.001), and they were statistically equivalent, with mean time to initial response at 8.4 weeks for patients receiving leflunomide vs 9.5 weeks for patients receiving methotrexate therapy. X-ray analyses demonstrated less disease progression with leflunomide (P=.001) and methotrexate (P = .02) therapy than with placebo. Leflunomide and methotrexate treatment improved measures of physical function and health-related quality of life significantly more than placebo (P<.001 and P<.05, respectively). Common adverse events for patients receiving leflunomide treatment included gastrointestinal complaints, skin rash, and reversible alopecia. Asymptomatic transaminase elevations resulted in treatment discontinuations for 7.1% of patients receiving leflunomide therapy, 1.7% of patients receiving placebo, and 3.3% of patients receiving methotrexate therapy. CONCLUSIONS: Clinical responses following administration of leflunomide, a new therapeutic agent for the treatment of RA, were statistically superior to those with placebo and equivalent to those with methotrexate treatment. Both active treatments improved signs and symptoms of active RA, delayed disease progression as demonstrated by x-ray films, and improved function and health-related quality of life.

Adult↗
PubMed1999

Cytosolic phospholipase A2 is induced in reactive glia following different forms of neurodegeneration.

Many recent studies have emphasized the deleterious role of inflammation in CNS injury. Increases in free fatty acids, eicosanoids, and products of lipid peroxidation are known to occur in various conditions of acute and chronic CNS injury, including cerebral ischemia, traumatic brain injury, and Alzheimer's disease. Although an inflammatory response can be induced by many different means, phospholipases, such as cytosolic phospholipase A(2) (cPLA(2)), may play an important role in the production of inflammatory mediators and in the production of other potential second messengers. cPLA(2) hydrolyzes membrane phospholipids and its activity liberates free fatty acids leading directly to the production of eicosanoids. We investigated the cellular localization of cytosolic phospholipase A(2) in the CNS following: (1) focal and global cerebral ischemia, (2) facial nerve axotomy, (3) human cases of Alzheimer's disease, (4) transgenic mice overexpressing mutant superoxide dismutase, a mouse model of amyotrophic lateral sclerosis, and (5) transgenic mice overexpressing mutant amyloid precursor protein, which exhibits age-related amyloid deposition characteristic of Alzheimer's disease. We show that in every condition evaluated, cytosolic phospholipase A(2) is present in reactive glial cells within the precise region of neuron loss. In conditions where neurons did not degenerate or are protected from death, cytosolic phospholipase A(2) is not observed. Both astrocytes and microglial cells are immunoreactive for cytosolic phospholipase A(2) following injury, with astrocytes being the most consistent cell type expressing cytosolic phospholipase A(2). The presence of cytosolic phospholipase A(2) does not merely overlap with reactive astroglia, as reactive astrocytes were observed that did not exhibit cytosolic phospholipase A(2) immunoreactivity. In most conditions evaluated, inflammatory processes have been postulated to play a pivotal role and may even participate in neuronal cell death. These results suggest that cytosolic phospholipase A(2) may prove an attractive therapeutic target for neurodegeneration.

Alzheimer Disease↗
PubMed1999

The changing faces of a parotid mass.

The development of a neurofibroma in the temporal and parotid regions of the facial nerve is rare. We report a case occurring in a 32-year-old male, where the initial presentation was a parotid mass. Cytologically this was initially thought to be a pleomorphic adenoma. However, the diagnosis was then changed to a schwannoma and finally a neurofibroma after complete excision of the lesion. The case illustrates how fine needle aspiration cytology under ultrasound guidance, and even histological examination of an incision biopsy can sometimes fail to give the correct diagnosis. In this case magnetic resonance imaging was used to help plan definitive surgery.

Adult↗
PubMed1999

The neuronal ceroid lipofuscinoses in human EPMR and mnd mutant mice are associated with mutations in CLN8.

The neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of progressive neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in various tissues. Progressive epilepsy with mental retardation (EPMR, MIM 600143) was recently recognized as a new NCL subtype (CLN8). It is an autosomal recessive disorder characterized by onset of generalized seizures between 5 and 10 years, and subsequent progressive mental retardation. Here we report the positional cloning of a novel gene, CLN8, which is mutated in EPMR. It encodes a putative transmembrane protein. EPMR patients were homozygous for a missense mutation (70C-->G, R24G) that was not found in homozygosity in 433 controls. We also cloned the mouse Cln8 sequence. It displays 82% nucleotide identity with CLN8, conservation of the codon harbouring the human mutation and is localized to the same region as the motor neuron degeneration mouse, mnd, a naturally occurring mouse NCL (ref. 4). In mnd/mnd mice, we identified a homozygous 1-bp insertion (267-268insC, codon 90) predicting a frameshift and a truncated protein. Our data demonstrate that mutations in these orthologous genes underlie NCL phenotypes in human and mouse, and represent the first description of the molecular basis of a naturally occurring animal model for NCL.

Amino Acid Sequence↗
PubMed1999

Seven year follow up of children presenting to the accident and emergency department with irritable hip.

OBJECTIVE: To assess an established protocol for managing children with irritable hip in the accident and emergency department. METHODS: Retrospective seven year follow up of all children managed under an established hip pain protocol. The main outcome measure was of failure of the protocol to identify serious pathology. RESULTS: A total of 103 children met the criteria for assessment using the protocol. Sixty were allowed home, and outpatient follow up arranged. All of these children except one were diagnosed as having transient synovitis. This child had Perthes' disease and was diagnosed at first presentation. Forty three children were admitted, with eight subsequently having a diagnosis other than transient synovitis of the hip. It was possible to review 80 children seven years later. Of these children no long term problems were encountered. CONCLUSION: The protocol used in the department for children with irritable hip is successful in identifying those children with transient synovitis of the hip, or other benign causes, and therefore not requiring hospital admission. Long term follow up showed that no serious pathology was missed.

Adolescent↗
PubMed1998

Reversal of renal failure and paraplegia after thoracoabdominal aneurysm repair.

Repair of ruptured thoracoabdominal aortic aneurysms is complicated by high rates of perioperative paraplegia, renal insufficiency, and mortality. This report describes a patient with a ruptured thoracoabdominal aortic aneurysm in whom preoperative acute renal failure was reversed with hemodialysis, aortic replacement, and renal revascularization. Prompt cerebrospinal fluid drainage reversed delayed-onset postoperative paraplegia and led to immediate, complete neurologic recovery.

Acute Kidney Injury↗
PubMed1997

Implementation of total quality management after reconfiguration of services on a general hospital unit.

In 1992 the New York State Office of Mental Health issued a statewide plan for mental health services to reduce the number of inpatient beds in state-run facilities from approximately 11,000 to between 6,000 and 8,000 by the year 2000. This reduction resulted in at least a 25 percent increase in psychiatric beds at local general hospitals. In 1992 Albany Medical Center Hospital's department of inpatient psychiatry established an interdisciplinary committee to address changes resulting from the reconfiguration of services to chronic mentally ill persons. The committee established procedures to use the principles of total quality management to respond to problems and to continuously improve the therapeutic milieu. The authors describe how these principles were used to create a patient satisfaction survey, to examine and improve part of the hospital admissions procedure, and to review and revise treatment planning documentation. A concurrent review committee reviews patients' records to ensure accuracy of documentation and quality of care.

Chronic Disease↗
PubMed1996

Multiple recurrent branch retinal artery occlusions associated with varicella zoster virus.

PURPOSE: The authors describe an immunocompetent patient who developed multiple recurrent branch retinal artery occlusions (BRAOs) associated with the varicella zoster virus (VZV). METHODS: A 69-year-old woman with mild bilateral vitritis developed superior and inferior BRAOs in her right eye with decreased visual acuity to 20/40, and a peripheral BRAO inferotemporally in her left eye. One month later, the inferotemporal BRAO progressed proximally in her left eye with a decrease of visual acuity to 20/40. After an extensive negative systemic evaluation, she underwent a diagnostic pars plana vitrectomy of her right eye. RESULTS: Vitreous fluid was positive for VZV DNA by polymerase chain reaction (PCR). The patient was treated with intravenous acyclovir and systemic oral steroids. After remaining disease free for 3 months, the patient had two recurrences: 1) a mild vitritis and 2) development of a new superior temporal artery occlusion in the left eye. Both recurrences were treated with oral acyclovir and systemic steroids. The patient remained recurrence free for 12 months on a maintenance dose of oral acyclovir, and for 4 additional months without acyclovir. CONCLUSIONS: Varicella zoster virus can be associated with the syndrome of multiple recurrent BRAOs. The diagnosis of VZV-associated BRAO can be established by PCR of intraocular fluid.

Acyclovir↗
PubMed1995

Linkage analysis of late-infantile neuronal ceroid-lipofuscinosis.

The neuronal ceroid-lipofuscinoses (NCL) are a group of neurodegenerative disorders with an autosomal-recessive pattern of inheritance. There are 3 main categories of childhood NCL, namely, infantile, late-infantile, and juvenile NCL. These can be distinguished on the basis of age of onset, clinical course, and histopathology. A number of variant forms of NCL have also been described, and these show symptoms intermediary between the main classical forms. The genes for both the infantile and juvenile forms of NCL have previously been mapped to chromosome areas 1p32 and 16p12, respectively. The gene for late-infantile NCL (LINCL), CLN2, has been excluded from both these loci, but its location is as yet unknown. Recently, CLN5, the gene for the Finnish variant form of LINCL, was mapped to 13q21.1-32. Using the 3 microsatellite markers which were most tightly linked to CLN5, we have excluded CLN2 from this region using a subset of 17 families. Thus, CLN2 represents a fourth distinct genetic locus involved in the pathogenesis of NCL.

Age of Onset↗