Search PubMed⌕ Search

Biomedical subjects

C O'Brien

Publications and source records attributed to C O'Brien.

At least 55 records · Page 3Linked to original sources
PubMed1998

Randomized, placebo-controlled study of tolcapone in patients with fluctuating Parkinson disease treated with levodopa-carbidopa. Tolcapone Fluctuator Study Group III.

OBJECTIVE: To assess the efficacy and tolerability of the catechol-O-methyltransferase inhibitor tolcapone in reducing "off/on" fluctuations in levodopa-treated parkinsonian patients. DESIGN: A randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Fifteen Parkinson disease clinics. PATIENTS: Two hundred fifteen referred outpatients with Parkinson disease who showed predictable end-of-dose motor fluctuations that were not controlled by a stable levodopa-carbidopa (Sinemet) regimen of at least 4 weeks' duration. INTERVENTIONS: In addition to their usual levodopa-carbidopa regimen, patients received placebo or tolcapone, 100 or 200 mg, 3 times daily orally for 6 weeks. PRIMARY OUTCOME MEASURE: Change in daily off/on time. RESULTS: Tolcapone, 100 and 200 mg 3 times daily, reduced off time by 2.0 and 2.5 hours per day, respectively, and increased on time by 2.1 and 2.3 hours per day, respectively (P<.001 vs placebo). Investigators' global measures of disease severity indicated that significantly more tolcapone-treated patients had reduced wearing off and symptom severity (P<.001 vs placebo). No significant change in quality-of-life measures occurred. Clinical improvements occurred despite a reduction in total daily levodopa dose of 185.5 mg (23%) in the tolcapone, 100 mg 3 times daily, group and 251.5 mg (29%) in the 200 mg 3 times daily group. Principal adverse events (mainly dyskinesia and nausea) were levodopa related, were not treatment limiting, and were seldom reported as reasons for withdrawal. The frequency of withdrawals because of adverse events was similar in all groups (3% to 7%). CONCLUSIONS: Tolcapone was well tolerated and substantially increased on time and reduced off time in patients with fluctuating Parkinson disease. Additionally, levodopa requirements were significantly decreased.

Aged↗
PubMed1998

A comparison of ocular blood flow in untreated primary open-angle glaucoma and ocular hypertension.

PURPOSE: To compare ocular blood flow in untreated primary open-angle glaucoma and ocular hypertension using scanning laser Doppler flowmetry and pulsatile ocular blood flow. METHOD: Fourteen ocular hypertensive subjects and 10 patients with primary open-angle glaucoma were matched for intraocular pressure, mean arterial blood pressure, and age. They had scanning laser Doppler flowmetry images taken centered on the optic disk. Pulsatile ocular blood flow readings were performed in sitting, standing, and supine positions. No subjects were receiving topical antiglaucoma treatment, systemic beta-blockers, calcium antagonists, or nitrates at the time of measurement. RESULTS: Laser Doppler flowmetry results showed a significant reduction in blood velocity, volume, and flow at the lamina cribrosa and the temporal neuroretinal rim in glaucoma compared to ocular hypertension (P < .05). No difference was found between the groups at the nasal neuroretinal rim or the nasal juxtapapillary retina. There was a significant increase in minimum velocity (P = .03) at the temporal juxtapapillary retina in glaucoma compared to ocular hypertension. The ocular pulse amplitude, pulse volume, and pulsatile ocular blood flow were significantly lower (P < .05) in the glaucoma group compared to ocular hypertension in sitting and standing positions. CONCLUSION: Having controlled for factors known to affect perfusion pressure, we found evidence of reduced ocular blood flow in primary open-angle glaucoma compared with ocular hypertension. Our findings indicate a reduction in choroidal and short posterior ciliary artery circulation in primary open-angle glaucoma. Whether these changes in blood flow are a cause or a consequence of glaucomatous optic atrophy is still unknown.

Aged↗
PubMed1998

Maintenance of pluripotential embryonic stem cells by stem cell selection.

As gastrulation proceeds, pluripotential stem cells with the capacity to contribute to all primary germ layers disappear from the mammalian embryo. The extinction of pluripotency also occurs during the formation of embryoid bodies from embryonic stem (ES) cells. In this report we show that if the initial differentiated progeny are removed from ES cell aggregates, further differentiation does not proceed and the stem cell population persists and expands. Significantly, the presence of even minor populations of differentiated cells lead to the complete loss of stem cells from the cultures. This finding implies that the normal elimination of pluripotent cells is dictated by inductive signals provided by differentiated progeny. We have exploited this observation to develop a strategy for the isolation of pluripotential cells. This approach, termed stem cell selection, may have widespread applicability to the derivation and propagation of stem cells.

Animals↗
PubMed1998

Telemetry pill measurement of core temperature in humans during active heating and cooling.

PURPOSE: This study compared the agreement between core temperature measurements obtained using an ingestible temperature pill telemetry system (Tpill) with those obtained from rectal (Tre) and esophageal (Tes) thermocouples under conditions of increasing and decreasing body temperature. METHODS: Four men and five women (age 25+/-2 yr, BSA 1.81+/-0.05 m2, VO2 peak 3.1+/-0.4 L x min[-1]) participated in four 3-h trials: cold (18 degrees C) water rest (CWR), cold water exercise (CWE), warm (36 degrees C) water rest (WWR), and warm water exercise (WWE). Subjects were immersed to the neck for each trial. During resting trials, subjects sat quietly. During exercise trials, subjects completed three bouts of 15 min of rest, followed by 45 min of exercise on a cycle ergometer at 50% of peak oxygen uptake. The temperature pill was taken 10-12 h before testing, after which the subjects fasted. RESULTS: The trials created conditions of constantly decreasing (CWR) or increasing (WWR) core temperature, as well as periods of oscillating core temperature (CWE and WWE). Root mean squared deviation (RMSD) was calculated for each pair of measurements (Tpill vs Tre, Tpill vs Tes, Tre vs Tes) for each trial. An RMSD of "0" indicates perfect agreement; as RMSD increases, agreement worsens. On CWR, the RMSD for Tpill-Tes (0.23+/-0.04) was lower (P < 0.05) than for Tpill-Tre (0.43+/-0.10) or Tre-Tes (0.46+/-0.09). There were no significant differences in RMSD between measurement pairs on any other trial (average RMSD = 0.26 degrees C). Telemetry pill temperature and response time tended to be intermediate between Tre and Tes. CONCLUSION: These results suggest the telemetry pill system provides a valid measurement of core temperature during conditions of decreasing as well as increasing body temperature and during steady state.

Adult↗
PubMed1998

Possible role for nitric oxide releasing nerves in the regulation of ocular blood flow in the rat.

AIM: To investigate the role of nitrergic nerves in the regulation of ocular blood flow. METHODS: Conscious, lightly restrained rats were treated with either the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI), or the nonselective inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), and ocular blood flow was measured ex vivo from tissue samples, using the fully quantitative [14C]-iodoantipyrine technique. RESULTS: In the peripheral circulation, L-NAME produced an increase in arterial blood pressure (+22%) while 7-NI had no effect. In contrast, both 7-NI and L-NAME produced significant decreases in ocular blood flow (-31% and -59% respectively). The ocular vascular resistance calculated from ocular blood flow and mean arterial blood pressure increased by 29% following 7-NI, but by 130% following L-NAME. CONCLUSIONS: Nitric oxide releasing neurons may play an important contributory role in regulating ocular blood flow.

Animals↗
PubMed1998

Pulsatile ocular blood flow investigation in asymmetric normal tension glaucoma and normal subjects.

AIMS: This study was designed to investigate pulsatile ocular blood flow (POBF) in normal tension glaucoma (NTG) patients and in normal controls. NTG patients with unilateral field loss were evaluated to compare POBF values between eyes with and without field loss. METHODS: POBF measurements from more than 1500 subjects were collected during a period of 6 months from six optometric centres. Subjects with systemic vascular diseases (such as systemic hypertension and diabetes), ophthalmic diseases, a positive family history of glaucoma, and those individuals receiving treatment with systemic beta blockers were excluded on the basis of a questionnaire. For comparison, 95 NTG patients with unilateral field loss, selected from 403 consecutive patients with NTG, underwent POBF testing. For each individual age, sex, intraocular pressure, refraction, and pulse rate were entered into a database. RESULTS: Data from 777 subjects were included in the analysis. POBF measurements of patients and subjects were compared allowing for differences in age, sex, intraocular pressure, refraction, and pulse rate. POBF was significantly lower in eyes of NTG patients with and without field loss (p < 0.001 and p = 0.01 respectively). Eyes of NTG patients with field loss showed significantly lower POBF than the contralateral eyes with normal field (p < 0.001). CONCLUSIONS: POBF was significantly lower in eyes of NTG patients with and without field loss than in normal subjects, suggesting that differences in ocular blood perfusion are relevant to the development of NTG and are detectable from the early stage of the disease. Furthermore, the finding of lower POBF in NTG eyes with field loss than in the contralateral eyes with normal field suggests that haemodynamic differences between fellow eyes contribute to determine the side of onset of the disease.

Adolescent↗
PubMed1998

Hypohydration and thermoregulation in cold air.

This study examined the effects of hypohydration on thermoregulation during cold exposure. In addition, the independent influences of hypohydration-associated hypertonicity and hypovolemia were investigated. Nine male volunteers were monitored for 30 min at 25 degrees C, then for 120 min at 7 degrees C, under three counterbalanced conditions: euhydration (Eu), hypertonic hypohydration (HH), and isotonic hypohydration (IH). Hypohydration was achieved 12 h before cold exposure by inducing sweating (HH) or by ingestion of furosemide (IH). Body weight decrease (4.1 +/- 0.2%) caused by hypohydration was similar for HH and IH, but differences (P < 0.05) were found between HH and IH in plasma osmolality (292 +/- 1 vs. 284 +/- 1 mosmol/kgH2O) and plasma volume reduction (-8 +/- 2 vs. -18 +/- 3%). Heat debt (349 +/- 14 among) did not differ (P > 0.05) among trials. Mean skin temperature decreased throughout cold exposure during Eu but plateaued after 90 min during HH and IH. Forearm-finger temperature gradient tended (P = 0.06) to be greater during Eu (10.0 +/- 0.7 degrees C) than during HH or IH (8.9 +/- 0.7 degrees C). This suggests weaker vasoconstrictor tone during hypohydration than during Eu. Final mean skin temperature was higher for HH than for Eu or IH (23.5 +/- 0.3, 22.6 +/- 0.4, and 22.9 +/- 0.3 degrees C, respectively), and insulation was lower on HH than on IH (0.13 +/- 0.01 vs. 0.15 +/- 0.01 degree C.W-1.m-2, respectively), but not with Eu (0.14 +/- 0.01 degree C.W-1.m-2). This provides some evidence that hypertonicity impairs the vasoconstrictor response to cold. Although mild hypohydration did not affect body heat balance during 2-h whole body exposure to moderate cold, hypohydration-associated hypertonicity may have subtle effects on vasoconstriction that could become important during a more severe cold exposure.

Adult↗
PubMed1998

Exertional fatigue, sleep loss, and negative energy balance increase susceptibility to hypothermia.

The purpose of this study was to determine how chronic exertional fatigue and sleep deprivation coupled with negative energy balance affect thermoregulation during cold exposure. Eight men wearing only shorts and socks sat quietly during 4-h cold air exposure (10 degreesC) immediately after (<2 h, A) they completed 61 days of strenuous military training (energy expenditure approximately 4,150 kcal/day, energy intake approximately 3,300 kcal/day, sleep approximately 4 h/day) and again after short (48 h, SR) and long (109 days, LR) recovery. Body weight decreased 7.4 kg from before training to A, then increased 6.4 kg by SR, with an additional 6.4 kg increase by LR. Body fat averaged 12% during A and SR and increased to 21% during LR. Rectal temperature (Tre) was lower before and during cold air exposure for A than for SR and LR. Tre declined during cold exposure in A and SR but not LR. Mean weighted skin temperature (Tsk) during cold exposure was higher in A and SR than in LR. Metabolic rate increased during all cold exposures, but it was lower during A and LR than SR. The mean body temperature (0.67 Tre + 0.33 Tsk) threshold for increasing metabolism was lower during A than SR and LR. Thus chronic exertional fatigue and sleep loss, combined with underfeeding, reduced tissue insulation and blunted metabolic heat production, which compromised maintenance of body temperature. A short period of rest, sleep, and refeeding restored the thermogenic response to cold, but thermal balance in the cold remained compromised until after several weeks of recovery when tissue insulation had been restored.

Body Composition↗
PubMed1998

Measuring tidal volume and functional residual capacity change in sleeping infants using a volume displacement plethysmograph.

The noninvasive measurement of infant lung function during unsedated sleep in infants has been a long-standing objective in paediatric respiratory medicine. This note reports on the design and performance of a head-out volume-displacement plethysmograph (VDP) that overcomes some of the limitations of traditional lung function apparatus. The VDP comprises a rigid acrylic box with an integral water-sealed spirometer and a novel neck seal. The bilayer neck seal is of variable compliance and is comfortable and simple to use. The spirometer permits volume resolution of 1.5 mL and a dynamic range in excess of 100 mL. The frequency response extends from 0-7 Hz. Spirometer inertance was measured as 0.0015 kPa.L(-1).s(-2), resistance 0.021 kPa.L(-1).s(-1) and box capacitance 0.18L.kPa(-1). Tidal volume, respiratory rate and changes in functional residual capacity can be recorded during unsedated rapid eye movement and nonrapid eye movement whilst monitoring with conventional polysomnographic methods. The head-out configuration allows additional instrumentation to be implemented with ease, avoids facial stimulation and allows unimpeded access to the upper airway. A polysomnograph illustrating the limitations of respiratory inductance plethysmography signals and typical changes in functional residual capacity are shown.

Functional Residual Capacity↗
PubMed1998

Serotyping scheme for Staphylococcus aureus isolated from cows with mastitis.

OBJECTIVE: To identify the Staphylococcus aureus capsular serotypes that are not typable, using capsular serotypes 5 and 8, which are currently used to type S aureus isolated from cows with mastitis. SAMPLE POPULATION: Milk samples (n = 273) from cows with mastitis in 178 dairy herds in California, Wisconsin, Michigan, Texas, and New York that were collected by state diagnostic laboratories and S aureus-positive milk samples collected by Veterinary Health Services in the United Kingdom (15), France (22), The Netherlands (36), and Germany (21). PROCEDURE: Capsular serotyping of coded isolates was performed by use of direct cell agglutination and immunoprecipitation of cell extracts with antisera specific for capsular types 5 and 8 and a newly developed S aureus serotyping antiserum 336. RESULTS: In the United States, S aureus capsular types 5 and 8 accounted for 18 and 23% of the isolates, respectively, and type 336 accounted for 59%. Percentage of capsular serotypes in European samples were as follows: type 5 = 34%, type 8 = 34%, type 336 = 30%, and nontypable = 2%. CONCLUSIONS: Serotypes 5 and 8 accounted for only 41% of S aureus isolates from US milk samples, but accounted for 70% of isolates from European milk samples. Addition of the newly developed serotyping antiserum 336 to the typing scheme accounted for 100% of US samples and 98% of European samples and will enable development of a more comprehensive S aureus vaccine.

Agglutination Tests↗
PubMed1997

A randomized, double-blind, placebo-controlled, phase III study of filgrastim in remission induction and consolidation therapy for adults with de novo acute myeloid leukemia. The International Acute Myeloid Leukemia Study Group.

The safety and efficacy of filgrastim as an adjunct to acute myeloid leukemia (AML) induction and consolidation therapy was assessed in this prospective double-blind, randomized, placebo-controlled, multicenter trial. A total of 521 consecutive de novo AML patients aged 16 or more years were randomized to receive filgrastim (5 microg/kg/d subcutaneously) or placebo after standard induction as well as consolidation chemotherapy. Blinded study drug was given from 24 hours after chemotherapy until the absolute neutrophil count was >/=1.0 x 10(9)/L for 3 consecutive days. The overall complete remission rate was 68%. After a median follow-up of 24 months (range 5 to 40) the median disease-free survival was 10 months (95% confidence interval [CI], 8.7 to 10.8) and the median overall survival was 13 months (95%CI, 12.2 to 14.6). These did not differ between treatment groups. Patients receiving filgrastim experienced neutrophil recovery 5 days earlier after induction 1 than those receiving placebo (P < .0001). This was accompanied by reductions in the duration of fever (7 v 8.5 days; P = .009), parenteral antibiotic use (15 v 18.5 days; P = .0001), and hospitalization (20 v 25 days; P = .0001). Similar reductions were seen after induction 2 and the consolidation courses. There was a significant reduction in the number of patients requiring systemic antifungal therapy in the filgrastim group during induction treatment (34% v 43%; P = .04). In conclusion, filgrastim is safe in that it had no negative impact on the prognosis of the AML patients. In addition, it effectively reduced the duration of neutropenia, leading to significant clinical benefits by reducing the duration of fever; requirement for parenteral anti-infectives, specifically amphotericin B; and the duration of hospitalization.

Adolescent↗