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Biomedical subjects

Christine Hunter

Publications and source records attributed to Christine Hunter.

18 recordsLinked to original sources
PubMed2007

Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders.

We sought to review the long-term tolerability of tetrabenazine (TBZ) and seek determinants of tolerability in the treatment of hyperkinetic movement disorders. A retrospective chart review was performed on patients treated with TBZ between 1997 and 2004. Efficacy of TBZ was assessed by a 1- to 5-point response scale (1 = marked reduction in abnormal movements, 5 = worsening). All adverse events (AEs) were captured according to their relationship with study drug. A total of 448 patients (42% male) were treated for a variety of hyperkinesias, including tardive dyskinesia (n = 149), dystonia (n = 132), chorea (n = 98), tics (n = 92), and myoclonus (n = 19). The mean age at onset of the movement disorder was 43.0 +/- 24.2 years, with TBZ starting at a mean age of 50.0 +/- 22.3 years. Patients remained on treatment for a mean of 2.3 +/- 3.4 years. An efficacy response rating of 1 or 2 was sustained in the majority of patients between the first and last visit. Common AEs included drowsiness (25.0%), Parkinsonism (15.4%), depression (7.6%), and akathisia (7.6%). Comparison of log-likelihood ratios revealed that age was a reliable predictor of Parkinsonism (P < 0.0001). TBZ is a safe and effective drug for the long-term treatment of hyperkinetic movement disorders.

Adult↗
PubMed2007

Short-term effects of tetrabenazine on chorea associated with Huntington's disease.

We sought to assess the short-term clinical effects of tetrabenazine (TBZ) on choreic movements in Huntington's disease patients. A total of 10 patients on stable doses of TBZ were enrolled in this observational study. Patients took their evening dose of TBZ and presented the next day to the Baylor College of Medicine Movement Disorders Clinic without taking the usual morning dose. They were assessed using the Unified Huntington's Disease Rating Scale (UHDRS) motor assessment and Beck Depression Inventory. The usual morning dose of TBZ was then administered and patients were followed with serial UHDRS motor examinations approximately every 2 hours until choreic movements subsided and then returned. TBZ decreased the UHDRS chorea score on average 42.4% +/- 17.8%. The duration of effect varied from a minimum of 3.2 hours to a maximum of 8.1 hours (mean = 5.4 +/- 1.3). No patient experienced an adverse event related to TBZ or its withdrawal. During short-term follow-up after a single dose, TBZ improves chorea for approximately 5 hours.

Adult↗
PubMed2007

Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families.

Mutations in the leucine-rich repeat kinase-2 gene (LRRK2) are responsible for some forms of familial as well as sporadic Parkinson's disease (PD). The purpose of this study was to examine the frequency of a single pathogenic mutation (6055G > A) in the kinase domain of this gene in United States and Tunisian familial PD and to compare clinical characteristics between patients with and without the mutation. Standardized case report forms were used for clinical and demographic data collection. We investigated the frequency of the most common substitution of LRRK2 (G2019S, 6055G>A) and its impact on epidemiological and phenotypic features. The frequency of mutations in Tunisian families was 42% (38/91) and in U.S. families 2.6% (1/39), with the unique opportunity to compare homozygous (n = 23) and heterozygous (n = 109) Tunisian carriers of G2019S substitutions. Individuals with G2019S substitutions had an older age at onset but few other differences compared with families negative for the substitution. Patients with LRRK2 mutations had typical clinical features of PD. Comparisons between individuals with heterozygous and homozygous LRRK2 mutations suggested that gene dosage was not correlated with phenotypic differences; however, the estimated penetrance was greater in homozygotes across all age groups.

Adult↗
PubMed2006

Effects of anti-VEGF antibody on blood-brain barrier disruption in focal cerebral ischemia.

Since cerebral ischemia increases expression of vascular endothelial growth factor (VEGF) and exogenous VEGF can aggravate BBB disruption in cerebral ischemia, we hypothesized that inhibition of endogenous VEGF would attenuate BBB disruption. To test this hypothesis, rats were mechanically ventilated with isoflurane and a craniotomy (5 mm in diameter) was performed to expose the cerebral cortex. Anti-VEGF antibody was applied topically (75 mug) 1 h before middle cerebral artery (MCA) occlusion and additional anti-VEGF antibody was applied (25 mug) immediately after MCA occlusion (anti-VEGF group). For the control animals, normal saline was applied instead of anti-VEGF antibody on the surface of the cortex (control group). One hour after MCA occlusion, the transfer coefficient (K(i)) of (14)C-alpha-aminoisobutyric acid and volume of (3)H-dextran (70,000 Da) distribution were determined to measure the degree of BBB disruption. There was no significant difference in vital signs, blood gases, and pericranial temperature between the control and the anti-VEGF group. In both of the groups, the K(i) of the ischemic cortex (IC) was higher than that of the corresponding contralateral cortex (CC) (p<0.05). The K(i) of the IC of the anti-VEGF group was significantly lower than that of the IC of the control group (-34%, p<0.05). The K(i) of the CC and pons were similar between these two groups. The data of volume of dextran distribution followed the same pattern as that of K(i) but without a statistical significance. Our data demonstrated that inhibition of endogenous VEGF by topical application of anti-VEGF antibody in the ischemic cortex decreased the K(i) of (14)C-AIB and suggest that endogenous VEGF is in part responsible for the BBB disruption during the early stage of focal cerebral ischemia.

Administration, Topical↗
PubMed2006

Comparing knowledge and attitudes towards genetic testing in Parkinson's disease in an American and Asian population.

INTRODUCTION: Recent discoveries of disease-causing genes in Parkinson's disease (PD) have generated considerable interest regarding genetic testing in PD. The attitudes toward genetic testing are largely influenced by knowledge and preconceived notions. OBJECTIVE: We investigated the relationship between knowledge of and attitude towards predictive genetic testing of PD in two independent centers in America and Asia involving PD patients and caregivers. METHODS: In a prospective study involving 515 subjects comprising of PD patients and their caregivers in two independent centers in America and Asia, the level of knowledge about genetic testing and patients' attitudes towards such testing were evaluated using a standardized questionnaire. RESULTS: American PD patients had a higher level of knowledge of PD genetics than Asian PD (31.1% vs. 12.3%, p=0.0002). A greater number of American PD patients and caregivers reported a positive attitude towards the potential medical benefits of genetic testing compared to their Asian counterparts (85.4% vs. 42.2%, 92.2% vs. 32.1%, p<0.00005), but a more negative attitude towards potential compromise in getting health and life insurance (43.7% vs. 25.8%, p=0.0002). However, in the Asian cohort, multivariate analysis revealed that a high level of genetics knowledge was associated with a positive attitude response regarding the potential medical benefits of testing (p<0.0005), but a negative attitude towards compromises in healthcare and life insurance, getting a job and starting a family (p<0.0005). These associations were not observed amongst American subjects. CONCLUSIONS: The relationship between level of genetic knowledge and attitude towards potential risks and benefits of predictive genetic testing in PD was distinctly different in two independent, racially and culturally different PD populations and caregivers. These observations have clinical implications in the development of PD genetic counseling programs.

Adult↗
PubMed2006

Trans-acting siRNA-mediated repression of ETTIN and ARF4 regulates heteroblasty in Arabidopsis.

Mutations in the ARGONAUTE gene ZIPPY(ZIP)/AGO7 in Arabidopsis accelerate the juvenile-to-adult transition. A screen for mutations that suppress this precocious phenotype yielded alleles of two auxin-related transcription factors known to be upregulated in zip: ETTIN (ETT)/ARF3 and ARF4. Mutations in ETT/ARF3 and ARF4 delay the expression of adult traits, demonstrating that these genes have non-redundant roles in shoot maturation. ZIP is not generally required for the production of trans-acting (ta) siRNAs, but is required for the production and/or stability of tasiR-ARF, a ta-siRNA that targets both ETT/ARF3 and ARF4. tasiR-ARF is absent in zip-2, and overexpression of a tasiR-ARF-insensitive form of ETT mimics the zip phenotype. We conclude that the precocious phenotype of zip is attributable to the absence of tasiR-ARF-mediated repression of ETT and ARF4. The abundance of tasiR-ARF, ETT/ARF3 and ARF4 RNA does not change during vegetative development. This result suggests that tasiR-ARF regulation establishes the threshold at which leaves respond to a temporal signal, rather than being a component of this signal.

Arabidopsis↗
PubMed2005

El Camino Hospital: using health information technology to promote patient safety.

BACKGROUND: El Camino Hospital is a leader in the use of health information technology to promote patient safety, including bar coding, computerized order entry, electronic medical records, and wireless communications. OVERALL APPROACH TO QUALITY AND SAFETY: Each year, El Camino Hospital's board of directors sets performance expectations for the chief executive officer, which are tied to achievement of local, regional, and national safety and quality standards, including the six Institute of Medicine quality dimensions. He then determines a set of explicit quality goals and measurable actions, which serve as guidelines for the overall hospital. The goals and progress reports are widely shared with employees, medical staff, patients and families, and the public. ADDRESSING THE SIX IOM QUALITY AIMS: For safety, for example, the medication error reduction team tracks and reviews medication error rates. The hospital has virtually eliminated transcription errors through its 100% use of computerized physician order entry. Clinical pathways and standard order sets have reduced practice variation, providing a safer environment. CHALLENGES: Many projects focused on timeliness, such as emergency department wait time, lab turnaround time, and pneumonia time to initial antibiotic. Results have been mixed, with projects most successful when a link was established with patient outcomes, such as in reducing time to percutaneous transluminal coronary angioplasty for patients with acute myocardial infarction.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Effects of VEGF and nitric oxide synthase inhibition on blood-brain barrier disruption in the ischemic and non-ischemic cerebral cortex.

OBJECTIVES: This study was performed to compare the effects of exogenous vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS) inhibition on blood-brain barrier (BBB) disruption in the ischemic cortex (IC) and non-ischemic contralateral cortex (CC) during the early stage of focal cerebral ischemia in rats. METHODS: A middle cerebral artery (MCA) was occluded after a craniotomy in each rat under isoflurane anesthesia. Two more craniotomies were performed over the contralateral non-ischemic hemisphere to expose cerebral cortex. For the control rats, the normal saline patches were applied to all three craniotomy holes (control group). To inhibit NOS, NG-nitro-L-arginine-methyl ester (L-NAME) (10 mg/kg) was administered i.v. 20 minutes after MCA occlusion (L-NAME group). In another group, VEGF (10(-10) M) was topically applied 30 minutes after MCA occlusion on the IC as well as one of the holes of the contralateral cortex (VEGF group). To investigate the effects of the combination of VEGF and L-NAME, both L-NAME and VEGF were administered as described above (L-NAME+ VEGF group). The transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid and the volume of 3H-dextran (70 000 Da) distribution were determined to measure the degree of BBB disruption at 1 hour after MCA occlusion. RESULTS: In the control group, Ki of the IC was significantly higher than the contralateral cortex (CC) (p<0.005). VEGF application increased the Ki of the IC further when compared with the control group (+51%, p<0.05%). L-NAME administration produced no significant decrease in the Ki of the IC when compared with the control group. With L-NAME+ VEGF administration, the Ki of the IC became significantly lower than that of the VEGF alone (-38%, p<0.005). Thus, L-NAME produced a much greater decrease in the Ki of the IC in the VEGF treated than the control animals (p<0.05). In the non-IC, VEGF, L-NAME, or their combination did not affect BBB disruption. The volume of dextran distribution followed a similar pattern to Ki. DISCUSSION: Our data suggest that even in the early stage of focal cerebral ischemia, the degree of BBB disruption in response to the exogenous VEGF is much greater in the ischemic than in the non-IC and that the mechanism of the increase of BBB disruption by VEGF in the IC involves the NOS pathway.

Administration, Topical↗
PubMed2004

A double-blind placebo-controlled trial of botulinum toxin B for sialorrhea in Parkinson's disease.

BACKGROUND: Injections of botulinum toxin A are an effective treatment for sialorrhea in Parkinson's disease (PD). Based on the relatively high rates of dry mouth seen with botulinum toxin B, there is reason to suspect that it may also improve sialorrhea. OBJECTIVE: To determine whether botulinum toxin B (Myobloc; Elan Pharmaceuticals, New York, NY) is a safe and effective treatment for sialorrhea in patients with PD. METHODS: Demographics, PD treatments, head posture, the Unified Parkinson's Disease Rating Scale (UPDRS), two questionnaires regarding drooling, Visual Analogue Scale, global impressions, salivary gland imaging, and a dysphagia questionnaire were assessed in 16 PD subjects with problematic sialorrhea. Patients were then randomized to receive either botulinum toxin B (1,000 units into each parotid gland and 250 units into each submandibular gland) or a pH-matched placebo, using only anatomic landmarks. Patients returned 1 month later to undergo an identical assessment. RESULTS: Compared with placebo, those randomized to drug reported improvement on the Visual Analogue Scale (p < 0.001), global impressions of change (p < 0.005), Drooling Rating Scale (p < 0.05), and Drooling Severity and Frequency Scale (p < 0.001). There was no change in UPDRS, head posture, or Dysphagia Scale. Adverse events were mild and included dry mouth (three patients), worsened gait (two), diarrhea (one), and neck pain (one) in the botulinum toxin B group. CONCLUSION: Anatomically guided injections of botulinum toxin B into the parotid and submandibular glands appear to effectively improve sialorrhea without compromising dysphagia in patients with PD.

Aged↗
PubMed2004

ReFUSing to grow up.

At germination, plants must coordinate the exit from dormancy and the start of vegetative growth. In this issue of Developmental Cell, Gazzarrini et al. show that FUSCA3 plays a critical role in regulating hormone levels to synchronize the transition from embryonic to vegetative growth in Arabidopsis.

Arabidopsis↗
PubMed2003

The Arabidopsis heterochronic gene ZIPPY is an ARGONAUTE family member.

Plants progress through a temporal sequence of juvenile, adult, and reproductive phases, each marked by the expression of phase-specific traits. Here we show that loss-of-function mutations in ZIPPY (ZIP) cause the premature expression of adult vegetative traits but do not accelerate the onset of reproductive competence or flowering time. ZIP encodes ARGONAUTE7 (AGO7), one of ten members of the ARGONAUTE family in Arabidopsis. In addition to playing developmental roles, some ARGONAUTE family members are required for RNAi-like phenomena, such as posttranscriptional gene silencing. In contrast to Arabidopsis ARGONAUTE1, ZIP has no significant role in transgene silencing; its primary function is in the regulation of developmental timing.

Arabidopsis↗
PubMed2003

Flumazenil, a GABA antagonist, may improve features of Parkinson's disease.

Manipulation of gamma-aminobutyrate (GABA) system has been little studied in Parkinson's disease, despite the fact that GABA subserves a large part of the basal ganglia, including the outflow tracts. To test whether antagonism of GABA could improve features of PD, we administered open label intravenous flumazenil to eight practically defined off patients and assessed UPDRS scores, bilateral 1-minute hand-tapping speed, and timed gait tests. Patients demonstrated significantly greater tapping speed, which peaked 40 minutes after injection (P < 0.05). Total motor Unified Parkinson's Disease Rating Scale scores modestly improved (P < 0.05). There were no adverse events. Mechanisms by which flumazenil could improve PD are discussed.

Aged↗
PubMed2003

miSSING LINKS: miRNAs and plant development.

The discovery of hundreds of plant micro RNAs (miRNAs) has triggered much speculation about their potential roles in plant development. The search for plant genes involved in miRNA processing has revealed common factors such as DICER, and new molecules, including HEN1. Progress is also being made toward identifying miRNA target genes and understanding the mechanisms of miRNA-mediated gene regulation in plants. This work has lead to a reexamination of many previously characterized mutations that are now known to affect components or targets of miRNA-mediated pathways.

Arabidopsis Proteins↗
PubMed2003

HASTY, the Arabidopsis ortholog of exportin 5/MSN5, regulates phase change and morphogenesis.

Loss-of-function mutations of HASTY (HST) affect many different processes in Arabidopsis development. In addition to reducing the size of both roots and lateral organs of the shoot, hst mutations affect the size of the shoot apical meristem, accelerate vegetative phase change, delay floral induction under short days, adaxialize leaves and carpels, disrupt the phyllotaxis of the inflorescence, and reduce fertility. Double mutant analysis suggests that HST acts in parallel to SQUINT in the regulation of phase change and in parallel to KANADI in the regulation of leaf polarity. Positional cloning demonstrated that HST is the Arabidopsis ortholog of the importin beta-like nucleocytoplasmic transport receptors exportin 5 in mammals and MSN5 in yeast. Consistent with a potential role in nucleocytoplasmic transport, we found that HST interacts with RAN1 in a yeast two-hybrid assay and that a HST-GUS fusion protein is located at the periphery of the nucleus. HST is one of at least 17 members of the importin-beta family in Arabidopsis and is the first member of this family shown to have an essential function in plants. The hst loss-of-function phenotype suggests that this protein regulates the nucleocytoplasmic transport of molecules involved in several different morphogenetic pathways, as well as molecules generally required for root and shoot growth.

Amino Acid Sequence↗
PubMed2002

Olanzapine treatment for dopaminergic-induced hallucinations.

Atypical antipsychotic medications with lower affinities for D2 receptors are considered useful alternatives to treat drug-induced hallucinations in Parkinson's disease (PD). We conducted a double-blind, placebo-controlled, unforced titration, parallel design study (2:1 drug to placebo randomization ratio) using olanzapine (2.5-10 mg/day to effect) in 30 PD patients with drug-induced hallucinations. We performed an extensive battery of neuropsychological tests, the Unified Parkinson's Disease Rating Scale (UPDRS), assessments of on and off time at baseline and at 9 weeks after starting the medication. Sixteen patients on olanzapine (mean dose, 4.6 mg/night) and 11 on placebo completed the study. Compared with placebo, performance on the UPDRS item 2 (thought disorder), and a structured interview for hallucinations, both tended to improve on drug but neither reached statistical significance. A neuropsychological test battery did not show any significant differences. Total on UPDRS motor scores (P < 0.05) and timed tapping (P < 0.01) worsened while on drug compared to placebo. Bradykinesia (P < 0.01) and gait (P < 0.001) items on the UPDRS largely accounted for this deterioration. After completion of the study, 8 of 16 patients randomly assigned to drug continued olanzapine at a mean dose of 2.4 mg/day. However, at the last recorded visit only 5 of 24 (20.8%) of all patients exposed to drug (including those originally randomly assigned to placebo) remained on olanzapine. In patients with PD, low-dose olanzapine did not significantly improve hallucinations but did worsen motor function.

Aged↗
PubMed2002

Conserved domains of the Nullo protein required for cell-surface localization and formation of adherens junctions.

During cellularization, the Drosophila melanogaster embryo undergoes a transition from syncytial to cellular blastoderm with the de novo generation of a polarized epithelial sheet in the cortex of the embryo. This process couples cytokinesis with the establishment of apical, basal, and lateral membrane domains that are separated by two spatially distinct adherens-type junctions. In nullo mutant embryos, basal junctions fail to form at the onset of cellularization, leading to the failure of cleavage furrow invagination and the generation of multinucleate cells. Nullo is a novel protein that appears to stabilize the initial accumulation of cadherins and catenins as they form a mature basal junction. In this article we characterize a nullo homologue from D. virilis and identify conserved domains of Nullo that are required for basal junction formation. We also demonstrate that Nullo is a myristoylprotein and that the myristate group acts in conjunction with a cluster of basic amino acids to target Nullo to the plasma membrane. The membrane association of Nullo is required in vivo for its role in basal junction formation and for its ability to block apical junction formation when ectopically expressed during late cellularization.

Actins↗
PubMedDate not supplied

Is history of depression a contraindication to treatment with tetrabenazine?

OBJECTIVE: To determine whether a history of depression predisposes hyperkinetic patients treated with tetrabenazine (TBZ) to a recurrence or worsening of this symptom. METHODS: We retrospectively reviewed the charts of 518 patients treated with TBZ to determine the frequency of depression and other adverse events. Charts were screened for the preexistence, development, or exacerbation of depression during the course of treatment. RESULTS: The most common adverse events related to TBZ were somnolence (27.4%), depression (15.1%), parkinsonism (11.8%), and akathisia (8.9%); 78 patients (15.1%) experienced depression for the first time or an exacerbation of existing depression. Of those patients with no history of depression, 28 (11.4%) of 246 were newly diagnosed with depression. Patients with a documented history of depression experienced a significantly higher rate of worsening in 50 (18.4%) of 272 cases (P = 0.03). However, patients with a history of depression experienced more improvement of their hyperkinesia compared to those without a history of depression (P < 0.01). CONCLUSIONS: Depression, an adverse event of TBZ, is more likely to occur or worsen in patients with a preexisting history of depression.

Adolescent↗