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C O'Brien

Publications and source records attributed to C O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed2001

Alpha-CaMKII-dependent plasticity in the cortex is required for permanent memory.

Cortical plasticity seems to be critical for the establishment of permanent memory traces. Little is known, however, about the molecular and cellular processes that support consolidation of memories in cortical networks. Here we show that mice heterozygous for a null mutation of alpha-calcium-calmodulin kinase II (alpha-CaMKII+/-) show normal learning and memory 1-3 days after training in two hippocampus-dependent tasks. However, their memory is severely impaired at longer retention delays (10-50 days). Consistent with this, we found that alpha-CaMKII+/- mice have impaired cortical, but not hippocampal, long-term potentiation. Our results represent a first step in unveiling the molecular and cellular mechanisms underlying the establishment of permanent memories, and they indicate that alpha-CaMKII may modulate the synaptic events required for the consolidation of memory traces in cortical networks.

Animals↗
PubMed2001

The natural history of embouchure dystonia.

Focal task-specific dystonias are unusual disorders of motor control, often affecting individuals who perform complex repetitive movements. Musicians are especially prone to develop these disorders because of their training regimens and intense practice schedules. Task-specific dystonia occurring in keyboard or string instrumentalists usually affects the hand. In contrast, there have been few descriptions of musicians with task-specific dystonia affecting the muscles of the face and jaw. We report detailed clinical observations of 26 professional brass and woodwind players afflicted with focal task-specific dystonia of the embouchure (the pattern of lip, jaw, and tongue muscles used to control the flow of air into a mouthpiece). This is the largest and most comprehensively studied series of such patients. Patients developed embouchure dystonia in the fourth decade, and initial symptoms were usually limited to one range of notes or style of playing. Once present, dystonia progressed without remission and responded poorly to oral medications and botulinum toxin injection. Patients with embouchure dystonia could be separated by the pattern of their abnormal movements into several groups, including embouchure tremor, involuntary lip movements, and jaw closure. Dystonia not infrequently spread to other oral tasks, often producing significant disability. Effective treatments are needed for this challenging and unusual disorder.

Adolescent↗
PubMed2001

Cervical dystonia severity scale reliability study.

Cervical dystonia (CD) is characterized by sustained contractions of the neck musculature, resulting in abnormal head postures. The Cervical Dystonia Severity Scale (CDSS) was developed to provide a reliable measure of treatment response in patients with CD. The CDSS uses a protractor and wall chart to rate the severity of the head's deviation from neutral in each of three planes of motion (rotation, laterocollis, anterocollis/retrocollis), which is then scored in 5 degree intervals (1 degree to 5 degrees deviation = 1; 86 degree to 90 degrees deviation = 18). To test the reliability of the CDSS, four centers, each with two independent examiners, evaluated 42 patients with CD. At each site, each of the two examiners used the CDSS to evaluate the head position of each patient twice, on the same day, for a total of four evaluations. The kappa value for intra-examiner agreement was 0.94 (95% confidence limit of 0.900-0.972), indicating excellent intra-examiner reliability. The kappa value for interexaminer reliability was 0.79 for the first evaluation and 0.86 for the second evaluation (95% confidence limits of 0.668-0.920 and 0.790-0.920) indicating excellent interexaminer reliability. Thus, the CDSS was highly reliable in both intra-examiner and interexaminer scoring comparisons.

Adult↗
PubMed2001

Intensive voice treatment (LSVT) for patients with Parkinson's disease: a 2 year follow up.

OBJECTIVES: To assess long term (24 months) effects of the Lee Silverman voice treatment (LSVT), a method designed to improve vocal function in patients with Parkinson's disease. METHODS: Thirty three patients with idiopathic Parkinson's disease were stratified and randomly assigned to two treatment groups. One group received the LSVT, which emphasises high phonatory-respiratory effort. The other group received respiratory therapy (RET), which emphasises high respiratory effort alone. Patients in both treatment groups sustained vowel phonation, read a passage, and produced a monologue under identical conditions before, immediately after, and 24 months after speech treatment. Change in vocal function was measured by means of acoustic analyses of voice loudness (measured as sound pressure level, or SPL) and inflection in voice fundamental frequency (measured in terms of semitone standard deviation, or STSD). RESULTS: The LSVT was significantly more effective than the RET in improving (increasing) SPL and STSD immediately post-treatment and maintaining those improvements at 2 year follow up. CONCLUSIONS: The findings provide evidence for the efficacy of the LSVT as well as the long term maintenance of these effects in the treatment of voice and speech disorders in patients with idiopathic Parkinson's disease.

Aged↗
PubMed2001

Cold strain index applied to exercising men in cold-wet conditions.

A cold strain index (CSI) based on rectal (T(re)) and mean skin temperatures ((sk)) using data from seminude resting subjects has been proposed (Moran DS, Castellani JW, O'Brien C, Young AJ, and Pandolf KB. Am J Physiol Regulatory Integrative Comp Physiol 277: R556-R564, 1999). The current study determined whether CSI could provide meaningful data for clothed subjects exercising in the cold with compromised insulation. Ten men exercised in cold-wet conditions (CW) for 6 h before (D0) and after 3 days of exhaustive exercise (D3). Each hour of CW consisted of 10 min of standing in rain (5.4 cm/h, 5 degrees C air) followed by 45 min of walking (1.34 m/s, 5.4 m/s wind, 5 degrees C air). The change in T(re) across time was greater (P < 0.05) on D3 than on D0, and the change in (sk) was less (P < 0.05) on D3 than on D0. Although CSI increased across time, the index at the end of both trials (D3 = 4.6 +/- 0.6; D0 = 4.2 +/- 0.8) was similar (P > 0.05). Thus, while (sk) was 1.3 degrees C higher (P < 0.05) and T(re) was 0.3 degrees C lower (P < 0.05) on D3 than on D0, CSI did not discriminate the greater heat loss that occurred on D3. These findings indicate that when vasoconstrictor responses to cold are altered, such as after exhaustive exercise, CSI does not adequately quantify the different physiological strain between treatments. CSI may be useful for indicating increased strain across time, but its utility as a marker of strain between different treatments or studies is uncertain because no independent measure of strain has been used to determine to what extent CSI is a valid and reliable measure of strain.

Adult↗
PubMed2001

Changes in bronchial inflammation during acute exacerbations of chronic bronchitis.

There are little data describing noncellular changes in bronchial inflammation during exacerbations of chronic bronchitis. The relationship between sputum colour and airway inflammation at presentation has been assessed during an exacerbation in patients with chronic bronchitis and a primary care diagnosis of chronic obstructive pulmonary disease. Sputum myeloperoxidase, neutrophil elastase, leukotriene B4 (LTB4), interleukin-8 (IL-8), sol:serum albumin ratio and serum C-reactive protein were measured in patients presenting with an exacerbation and mucoid (n = 27) or purulent sputum (n = 42). Mucoid exacerbations were associated with little bronchial or systemic inflammation at presentation, and sputum bacteriology was similar to that obtained in the stable state. Purulent exacerbations were associated with marked bronchial and systemic inflammation (p < 0.025 for all features) and positive sputum cultures (90%). Resolution was related to a significant reduction in LTB4 (p < 0.01), but no change in IL-8, suggesting that LTB4 may be more important in neutrophil recruitment in these mild, purulent exacerbations. In the stable state, IL-8 remained higher in patients who had experienced a purulent exacerbation (2p < 0.02). The presented results indicate that exacerbations of chronic bronchitis, defined by sputum colour, differ in the degree of bronchial and systemic inflammation. Purulent exacerbations are related to bacterial infection, and are associated with increased neutrophilic inflammation and increased leukotriene B4 concentrations.

Acute Disease↗
PubMed2001

Renal function after pediatric cardiac transplantation: the effect of early cyclosporin dosage.

BACKGROUND: There is little data on renal function in pediatric heart transplant recipients. Early rejection is a major concern and most units run high cyclosporin A (CyA) levels during the 2 to 3 months after transplantation. We sought to document long-term renal function after transplantation and to assess influence of early CyA levels. METHODS: We reviewed all of our pediatric transplants between June 1985 and August 1998 who survived longer than 6 months (n = 54). Glomerular filtration rate (GFR) was estimated at 1, 2, 4, and 8 years posttransplantation using the Schwartz formula: GFR (mL/min/1.73m(2)) = [Ht(cm)/creatinine(micromol/L)] x X We also analyzed whether change in renal function correlated with trough CyA levels. RESULTS: Median age at transplant was 4 years and median follow-up was 5 years. Survival rates were 87% at 1 year and 80% at 5 years. Mean GFR pretransplant was 79 +/- 19 mL/min/1.73 m(2), reflecting prerenal impairment. One year later, mean GFR was 72 mL/min/1.73 m(2); after 2 years it was 65 mL/min/1.73 m(2), after 4 years (n = 35) it was 60 mL/min/1.73 m(2), and after 8 years (n = 14) it was 57 mL/min/1.73 m(2). CyA levels during the first 2 months correlated with the change in GFR during the first year (r(2) = 0.21). CONCLUSIONS: This study demonstrates for the first time that decline in renal function after heart transplantation correlates with early CyA exposure; this dysfunction persists even when CyA doses are subsequently reduced.

Child↗
PubMed2001

Impact of histological grade of hepatocellular carcinoma on the outcome of liver transplantation.

HYPOTHESIS: Histological grade of hepatocellular carcinoma (HCC) is an important prognostic factor affecting patient survival after orthotopic liver transplantation (OLT). DESIGN: Retrospective analysis. SETTING: University-based teaching hospital. PATIENTS: Of 952 OLTs performed between June 1991 and January 1999, 56 OLT recipients had histologically proven HCC in the explant liver. Of those, 53 patients with complete clinicopathologic data were analyzed. A single pathologist blinded to the outcome of each patient reviewed all histological specimens. RESULTS: Median follow-up was 709 days. Overall survival for patients with tumors sized 5 cm or less at 1, 3, and 5 years was 87%, 78%, and 71%, respectively (Kaplan-Meier). Univariate analysis revealed the size, number, and distribution of tumors; the presence of microscopic vascular invasion and lymph node metastasis; histological differentiation; and pTNM stage to be statistically significant factors affecting survival. Multivariate analysis revealed histological differentiation and pTNM stage to be the independent and statistically significant factors affecting survival (P =.002 and.03, respectively). When pTNM stage was excluded from multivariate analysis, histological differentiation and size remained the significant independent factors (P =.02 and.03, respectively). Three-year survival for patients with small (</=5 cm) tumor with well- to moderately differentiated and poorly differentiated HCC was 82% and 67%, respectively. Three-year survival for patients with large (>5 cm) tumor with well- to moderately differentiated and poorly differentiated HCC was 62.5% and 0%, respectively. CONCLUSIONS: In our retrospective experience, histological differentiation had a statistically significant effect on the prognosis of HCC after OLT. However, before altering the current OLT selection criteria for patients with HCC, prospective studies are required to confirm the impact of histological grade on clinical outcome.

Carcinoma, Hepatocellular↗
PubMed2000

Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases.

BACKGROUND: There is a clear and growing need for data regarding BRCA1 and BRCA2 mutation frequencies among breast carcinoma cases not specifically ascertained on the basis of extreme family history profiles. Toward this end, the authors previously reported results with regard to BRCA1 in breast carcinoma patients drawn from a population-based study. In the current study the authors present new findings concerning BRCA2 mutation frequency in this same population, as well as summary data regarding the combined contribution of these two genes. METHODS: Subjects were drawn from two population-based, case-control studies of breast carcinoma in young women conducted in western Washington State and focused on 1) women diagnosed with breast carcinoma before age 35 years (n = 203); and 2) women with a first-degree family history of breast carcinoma who were diagnosed before age 45 years (n = 225). Similarities and differences between BRCA2 carriers and BRCA1 carriers were analyzed in terms of age at diagnosis, family history status, and disease features. RESULTS: Of cases diagnosed before age 35 years, all of whom were unselected for family history, 9.4% carried germline mutations (3.4% for BRCA2 and 5.9% for BRCA1). Of cases diagnosed before age 45 years who had a first-degree family history of breast carcinoma, 12.0% carried germline mutations (4.9% for BRCA2 and 7.1% for BRCA1). Increased frequencies of mutations were observed in cases with a personal or family history of early age at diagnosis and in those with four or more family members affected with breast carcinoma. BRCA2 mutations were less common than BRCA1 mutations in families with any history of ovarian carcinoma. CONCLUSIONS: Overall, given current constraints on health care resources, these data suggest that screening for germline mutations in these breast carcinoma susceptibility genes may have the greatest impact on overall health care if it is prioritized toward high and moderate risk populations.

Adult↗
PubMed2000

Malignant spinal neurofibrosarcoma.

STUDY DESIGN: A report of a case of metastatic spinal neurofibrosarcoma. OBJECTIVE: To document metastatic neurofibrosarcoma as a cause of spinal cord compression and to review the literature. SUMMARY OF BACKGROUND DATA: Three previously reported cases of metastatic neurofibrosarcoma of the spine were reviewed. METHODS: The patient's clinical record and radiologic investigations as well as the result of a search of the English literature are reported. Magnetic resonance images, computed tomographic scans, and histology photomicrographs are displayed. RESULTS: Paraparesis developed in this patient, due to a posterior extradural thoracic spinal cord compression by a neurofibrosarcoma believed to be metastatic from a neurofibrosarcoma of the femoral nerve. CONCLUSIONS: Malignant spinal metastasis remains a rare complication of neurofibromatosis, with a very poor prognosis.

Fatal Outcome↗
PubMed2000

Obsessive-Compulsive Disorder and Tourette's Syndrome.

Obsessive-compulsive behavior (OCB) or full-blown obsessive-compulsive disorder (OCD) afflict more than 50% of patients with Tourette's syndrome (TS) and often are more debilitating than the tic disorder itself. Medications for OCD, including selective serotonin reuptake inhibitors (SSRIs), help patients with TS and OCD, particularly in combination with low-dose antipsychotic drugs, but seldom eliminate OCD entirely. Behavioral therapies are more effective as medications for the treatment of OCD. A combination of cognitive behavioral therapy and medication is the treatment of choice for most patients with TS and OCD.

Journal Article↗
PubMed2000

Colour Doppler imaging of the ocular circulation in diabetic retinopathy.

PURPOSE: To measure blood flow velocity in the ophthalmic artery (OA) and central retinal artery (CRA) in patients with diabetic retinopathy. SUBJECTS AND METHODS: 62 age-matched subjects divided into 3 groups: nondiabetic controls (n=17); diabetics with no clinical retinopathy or background changes (n=24); diabetics with either pre-proliferative or proliferative retinopathy (n=21). Colour Doppler imaging was performed on supine patients by one masked observer using the Acuson 128 machine. RESULTS: There was a statistically significant (p<0.05) decrease in both the peak systolic velocity (PSV 0.073 m/s) and end diastolic velocity (EDV 0.014 m/s) of the central retinal artery in the pre-proliferative/proliferative group compared to the no retinopathy/background retinopathy group (PSV 0.096 m/s, EDV 0.024 m/s) and the control group (PSV 0.142 m/s, EDV 0.029 m/s). The resistance index of the ophthalmic artery was significantly increased in both the preproliferative/proliferative (0.81) and the no retinopathy/background group (0.81) compared to controls (0.72). CONCLUSION: Reduced blood flow velocity was found in the CRA of diabetic patients and appeared to become further reduced with the progression of retinopathy. This suggests that monitoring with Colour Doppler imaging may have predictive power in identifying those at greatest risk of developing sight threatening proliferative disease. The resistance index of the OA was increased in diabetics compared to controls.

Aged↗
PubMed2000

Creating books for the National electronic Library for Health: expected barriers and useful lessons.

The National electronic Library for Health (NeLH) is now taking shape, as the virtual branch libraries begin to accumulate 'books', among their resources. In the Primary Care branch (http://www.nelh-pc.nhs.uk), one of the first available books was the Statement of Fees and Allowances (otherwise known as the Red Book). While being held up as an example of what the NeLH can offer, this book and the story of its transformation from paper to Internet format is a powerful example of how much further the National Health Service (NHS) must go before it can claim to be fully exploiting the benefits of information technology (IT). This article refers to the author's experience in producing electronic books for primary care using WaX software, and an example of a process change from paper to screen that was managed within a university administrative office. The author suggests that to reap optimal benefits from IT, the NeLH and its collaborators must address the fundamental issues of people and the paper-based processes used by information providers. The NeLH must work with both NHS IT trainers and information providers in a three-way collaboration involving key people and processes, to achieve the efficient production of an updateable and user-friendly library of electronic books.

Books↗