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Biomedical subjects

C O'Brien

Publications and source records attributed to C O'Brien.

At least 19 recordsLinked to original sources

Thrombocytopenia after liver transplantation.

BACKGROUND: Thrombocytopenia after orthotopic liver transplantation (OLT) is a well recognized and prevalent early postoperative complication. The etiology, as well as the effect of this phenomenon on transplant outcome, however, are vague. The aims of this study are to identify factors contributing to thrombocytopenia and to ascertain whether there is any correlation with early rejection and ultimate survival. METHODS: This study examines 541 OLTs (541 grafts in 494 patients) that were transplanted at the University of Miami during the 3-year period from June 1994 to September 1997. The patients with severe postoperative thrombocytopenia (nadir platelet count [PLT] < 20,000/mm3), as well as the whole group of patients, were analyzed. The preoperative PLT, intra-operative platelet transfusion requirements, cross-match, recipient and donor cytomegalovirus (CMV) status, infusion of donor bone marrow cells (DBMC), occurrence of early rejection episodes (in the first posttransplant month), and re-transplantation were factors examined for any association with thrombocytopenia. Total bilirubin (TB) and direct bilirubin (dB), hematocrit, white blood cell count (WBC), aspartate aminotransferase and alanine aminotransferase, determined on the day that platelets reached a nadir (nadir day), were also analyzed. RESULTS: In 90.9% of the cases, there was a 56.5%+/-23.5% fall in platelets in the immediate posttransplant period (first 2 weeks), but the mean PLT exceeded preoperative levels during the 3rd and 4th postoperative weeks. The nadir of the drop in the PLT most commonly occurred on posttransplant day 4. For preoperative PLT, platelet transfusions during the operation, re-transplantation, early rejection, cross-match, and recipient CMV status, there was significant statistical correlation with any degree of postoperative thrombocytopenia. Four of these factors, preoperative PLT, intra-operative platelet transfusions, re-transplantation, and early rejection, were found to be independently associated with thrombocytopenia in general. None of them was found to be independently correlated with severe thrombocytopenia. A statistically significant correlation between bilirubin and WBC on the nadir day and the degree of thrombocytopenia was observed. No correlation was found between infusion of DBMC or donor CMV serology and thrombocytopenia. Both the nadir PLT and the percentage of the platelet fall were independent predictive factors (p<0.01 and 0.005, respectively) of patient and graft survival. CONCLUSIONS: Thrombocytopenia in the immediate posttransplant period is correlated with low preoperative PLT, massive platelet transfusions, and re-transplantation. These factors reflect a poor preoperative condition. There is also a correlation with allograft dysfunction, rejection, and poorer patient and graft survival. A rise in the mean PLT after the 2nd postoperative week reflects proper graft function.

Adolescent

Patients' perception of visual impairment in glaucoma: a pilot study.

BACKGROUND/AIMS: There is a paucity of useful information on the level of visual disability suffered by glaucoma patients. The aims of this study were to determine and rank the frequency of self reported visual disability in daily tasks performed by glaucoma patients; to examine the interrelation between disabilities using factor analysis; to study the relation between perceived visual difficulty and a measure of the severity of visual field loss; to develop a glaucoma specific subgroup of questions; and examine the validity and reliability of this subgroup of questions. METHODS: 63 glaucoma patients completed a questionnaire containing 62 questions covering 10 broad aspects of daily life activities using a five point answer scale. Patients were classified into three groups as having mild, moderate, and severe field loss on the basis of the perimetric results. The relation between a measure of the severity of visual field loss and subjective visual disability in the three groups was examined. RESULTS: Using factor analysis, the most frequently reported problems were grouped into the following four categories: outdoor mobility, glare and lighting conditions and activities demanding functional peripheral vision, household tasks, and personal care. These four factors accounted for 72% of the variability in the patients' questionnaire responses. With increasing severity of binocular visual field loss there was an increase in the number of self reported visual problems. A loss of confidence in performing some routine daily tasks tended to precede self reported specific visual disabilities. The factor "glare and lighting and activities demanding functional peripheral vision" was found to have a significant relation with a measure of visual field loss and was used to create a glaucoma specific subset of questions. Cronbach's alpha showed a high degree of reliability and internal consistency (alpha =0.96) in this glaucoma specific subset of questions. Furthermore, the validity of this new subset of questions was shown to be significant (r=0.037, p<0.05) for the correlation between a measure of the severity of binocular visual field loss and the mean score of the variables used in the glaucoma specific subgroup of questions. CONCLUSIONS: Outcome measures and quality of life issues need to be addressed in glaucoma. This pilot study identified common problems encountered by patients which at the present time are not assessed in routine glaucoma care. It also identified a subgroup of questions that seems to be specific for glaucoma. Further research is required if a significant impact on the quality of life of glaucoma patients is to be achieved.

Aged

Blood flow velocity in the peripheral circulation of glaucoma patients.

Using the laser Doppler technique we measured finger blood flow velocity in 25 untreated primary open-angle glaucoma (POAG), 22 untreated low-tension glaucoma (LTG) and 19 age-matched normal subjects. Four blood flow measurements were recorded: baseline flow, after immersion in warm water for 2 min (40 degrees C maximum flow), after 10 s exposure to cold water (4 degrees C minimum flow) and time to recover to baseline flow after cold immersion. Significant differences between the LTG group and both the normal and POAG groups were found in a greater maximum flow (p = 0.03 and p = 0.01, respectively), a lower minimum flow (p = 0.04 and p = 0.03, respectively) and a longer recovery time to baseline flow (p = 0. 0001 for both the normal and POAG groups). A longer recovery time to baseline flow (p = 0.008) in POAG was the only difference between the normal and POAG groups. Both glaucoma groups had more systemic vascular disease than normal, and there were more smokers in the POAG group than normals. Subgroup assessment performed with migraine, vascular disease and smoking subjects excluded from the analysis did not alter the overall results. We conclude that systemic vasospasm is a strong feature of low-tension glaucoma.

Aged

The anatomy of a crisis. One perspective.

In this article, the author analyzes the influx of breast implant class action lawsuits in the past decade. He discusses the responses of the medical community and the manufacturers as well as the impact the media has had on this issue. The author recounts the steps he took in his representation of the defense and examines the significance of these lawsuits for the industry and the general public.

Breast Implantation

Growth of human tumor cells in macroporous microcarriers results in p53-independent, decreased cisplatin sensitivity relative to monolayers.

Multicellular contact has been shown to influence the in vitro sensitivity of cells to drug treatment. We investigated the use of macroporous gelatin microcarriers, CultiSpher-G, as a convenient laboratory system for the molecular analysis of this "contact effect". We determined that human A549 cells can be grown in CultiSphers with growth and cell cycle parameters similar to those of monolayers. In addition, cells in CultiSphers express less p27/kip1, an indicator of cell cycle arrest, than equivalent cells in monolayers. When treated with drugs, A549 cells grown in CultiSphers or monolayers accumulate equivalent amounts of platinum-DNA adducts and similar amounts of doxorubicin. Moreover, A549 and KB-3-1 cells in CultiSphers have significantly decreased sensitivity to cis-platinum(II)diammine dichloride (cisplatin), 4-hydroperoxycyclophosphamide, doxorubicin, and paclitaxel (taxol) compared with cells in monolayers when assayed by clonogenic survival. Cisplatin treatment in monolayers or CultiSphers did not result in apoptotic cell death. In contrast, paclitaxel caused a significant amount of sub-G1 DNA, an indicator of apoptosis, which was diminished when cells were grown in CultiSphers compared with monolayers. When grown in CultiSphers, cells with abrogated p53 function (A549/16E6 and NCI-H1299) were less sensitive to cisplatin than the corresponding monolayer cells, indicating that the decrease in sensitivity is p53 independent. Taken together, the data suggest that CultiSpher-G microcarriers are a useful in vitro system to examine the effects of three-dimensional cell contact on drug sensitivity of human tumor cells.

Antineoplastic Agents

A protective effect of apolipoprotein E e2 allele on dementia in Down's syndrome.

BACKGROUND: The apolipoprotein E (ApoE) e4 allele has been associated with an increased risk for Alzheimer's disease, whereas the e2 allele has been shown to be protective. Similar effects in Down's syndrome (DS) have been postulated but not yet demonstrated. METHODS: We obtained DNA from 221 DS individuals and from 162 population controls, and 77 DS children. Older DS subjects were evaluated for dementia and compared to age-matched DS controls. RESULTS: The DS sample with dementia (n = 31) had a significantly lower frequency of the ApoE e2 allele compared to age-matched nondemented DS controls (0% vs. 8.3%, p = .0136). The older DS population had a significantly lower frequency of ApoE e4 compared to population controls (11.7% vs. 20.6%, chi-square 8.9, p = .0028). CONCLUSIONS: The lower frequency of the e2 allele in demented DS subjects compared to age-matched nondemented DS controls suggests a protective effect for ApoE e2 in the development of dementia in DS. The lower frequency of ApoE e4 in our older DS sample compared to population controls points to a detrimental effect of the e4 allele on longevity.

Adult

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

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

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

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

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

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

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

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

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