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Biomedical subjects

C O'Connor

Publications and source records attributed to C O'Connor.

At least 19 recordsLinked to original sources
PubMed1997

Phase I and pharmacologic study of paclitaxel administered weekly in patients with relapsed ovarian cancer.

PURPOSE: Paclitaxel has shown significant activity in advanced ovarian cancer. In vitro studies with paclitaxel have suggested that fractionated brief infusion schedules may be more effective than the standard 24-hour infusion. We commenced a phase I evaluation of escalating-dose paclitaxel (40, 50, 60, 80, 100 mg/m2) administered weekly as a 1-hour infusion in patients with recurrent ovarian cancer. All patients had received prior paclitaxel and cisplatin therapy. All patients received standard premedication. PATIENTS AND METHODS: Eighteen patients are assessable on this phase I study. The mean age was 54 years (range, 48 to 74). The median number of prior chemotherapy regimens was three (range, two to five). The mean paclitaxel-free interval was 10.1 months (range, 1 to 24). RESULTS: A total of 194 cycles of therapy were administered, with a mean of 10 (range, one to 12) per patient. No mucositis or grade III neuropathy was seen. Alopecia occurred in one out of 18 assessable patients. The mean neutrophil nadir was 4.0 x 10(9)/L. At the top dose level (100 mg/m2) delivered, dose-intensity was 90.75% of that planned and greater than two fold the standard dose-intensity. Partial responses were seen in four of 13 assessable patients (30%). Two patients with progression of disease on standard three-week paclitaxel schedules switched to a weekly schedule with demonstrated response. Increasing paclitaxel dose correlated with measured area under the curve (AUC) (R2 = .614). Dose-limiting toxicity was reached at 100 mg/m2 with two of three patients experiencing a treatment delay, thus defining a maximum-tolerated dose of 80 mg/m2 in this group of heavily pretreated patients on this weekly schedule. CONCLUSION: (1) Paclitaxel administered as a 1-hour infusion is well tolerated; (2) this schedule of administration does not result in cumulative myelosuppression; and (3) this schedule of administration results in dose-intensive paclitaxel delivery with a favorable toxicity profile.

Adenocarcinoma, Clear Cell↗
PubMed1996

Chest trauma: the role of transesophageal echocardiography.

Aortic and cardiac injury is commonly seen with severe chest trauma and contributes to the morbidity and mortality of automobile accidents. Transesophageal echocardiography is emerging as an important diagnostic tool for the evaluation of cardiovascular injury in the setting of acute chest trauma, and anesthesiologists should be familiar with the echocardiographic features of these traumatic lesions.

Accidents, Traffic↗
PubMed1996

Neutrophil activation in fibrosing alveolitis: a comparison of lone cryptogenic fibrosing alveolitis and systemic sclerosis.

Fibrosing alveolitis complicating systemic sclerosis (FASSc) carries a better prognosis than lone cryptogenic fibrosing alveolitis (CFA). We wanted to determine whether this improved prognosis is associated with differential neutrophil migration and activation in the lower respiratory tract. We therefore compared bronchoalveolar lavage (BAL) neutrophil numbers and levels of neutrophil-derived enzymes in FASSc, CFA and normal individuals. Bronchoalveolar lavage was performed on 45 subjects (FASSc n = 20; CFA n = 15; normals n = 10); cell counts and levels of neutrophil-derived enzymes, myeloperoxidase, elastase (total elastase and elastase/alpha 1 antitrypsin complexes), collagenase and lactoferrin were measured. Lung function testing was performed in subjects with fibrosing alveolitis. Significant differences in the levels of collagenase, myeloperoxidase and elastase/ alpha 1-antitrypsin complexes were present in the BAL fluid from the three groups. Patients with CFA had significantly higher neutrophil percentages and levels of collagenase and myeloperoxidase than those with FASSc. Disease extent, as judged by lung volumes and gas transfer, was comparable in the CFA and FASSc groups. Forced vital capacity (% predicted) was significantly lower in patients with evidence of increased neutrophil enzyme release than those without. We conclude that: 1) increased neutrophil migration to the lung is accompanied by release both of primary and secondary granule enzymes in cryptogenic fibrosing alveolitis; and 2) the lower amounts of neutrophil products in fibrosing alveolitis complicating systemic sclerosis may account for the improved prognosis, even when disease is as extensive as in cryptogenic fibrosing alveolitis.

Adult↗
PubMed1993

Relation of cardiovascular responses to mental stress and cardiac vagal activity in coronary artery disease.

Forty-six patients with documented coronary artery disease were studied to examine the relation of cardiovascular reactivity to mental stress and cardiac vagal activity. Cardiac vagal activity was measured by means of frequency-domain analysis of heart rate variability with 48-hour out-of-hospital Holter monitoring. The amplitude of the high-frequency component (0.16 to 0.40 Hz) of heart rate variability is considered to be an index of cardiac vagal activity. Cardiovascular reactivity was measured in the laboratory during a 3-minute public speaking task. Results revealed that (1) the amplitude of the high-frequency component was significantly higher during sleep (24.6 +/- 11.3 ms) than during waking (18.2 +/- 8.0 ms) (p = 0.002); (2) compared to subjects with low diastolic blood pressure reactivity, those who displayed high diastolic blood pressure reactivity exhibited a significantly lower amplitude of the high-frequency component (19.2 +/- 6.9 vs 23.4 +/- 9.6 ms, p = 0.03). These results indicate that decreased cardiac vagal activity may contribute to the exaggerated diastolic blood pressure reactivity to mental stress in patients with coronary artery disease.

Aged↗
PubMed1992

N-methyl-D-aspartate receptor antagonist MK-801 and spatial memory representation: working memory is impaired in an unfamiliar environment but not in a familiar environment.

Female Sprague-Dawley rats were injected with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 or saline 30 min before daily testing in spatial working memory (WM) and reference memory (RM) procedures in an 8-arm radial maze. MK-801 impaired RM and WM acquisition but not performance when rats were trained to criterion before drug administration. Neither a 2-hr nor a 4-hr delay between the first and last 2 correct WM choices impaired long-term WM. MK-801 impaired WM performance in trained rats only when rats were tested in a new environment. Thus, 2 mechanisms may be required for relational memory: an NMDA-dependent mechanism for acquiring long-term spatial representations and an NMDA-insensitive mechanism for operating on these stored representations.

Animals↗
PubMed1991

Failure of adjuvant heparin to reduce myocardial ischemia in the early treatment of patients with unstable angina.

Although the efficacy of long-term administration of antithrombotic agents in unstable angina has been established, short-term effects on myocardial ischemia are unknown. A retrospective analysis was performed in 47 patients undergoing three-channel continuous ST segment monitoring as part of a multicenter trial using esmolol in unstable angina, in which 20 patients received a continuous heparin infusion during the initial assessment of chest pain. Concomitant medications included calcium channel blockers, beta-adrenergic blockers, nitrates, and aspirin in the majority of patients. Clinical variables between the heparin and no heparin groups were similar, except for fewer males and fewer total artery occlusions in the heparin group. No significant differences in the incidence or duration of ischemia were found in a 36 +/- 16 hour monitoring period. Forty percent of the heparin group had 35 episodes of ischemia with a mean of 11 +/- 10 minutes per episode and a total ischemic time of 48 +/- 39 minutes per patient with ischemia. Forty-four percent of the no heparin group had 47 episodes of ischemia with a mean of 13 +/- 13 minutes per episode and a total ischemic time of 58 +/- 47 minutes per patient with ischemia. Multiple linear regression analysis to adjust for intergroup differences did not alter the results. Eighty-five percent of all episodes were asymptomatic. Clinical events, such as episodes of chest pain, emergency coronary arteriography, or coronary revascularization, were also similar between groups. Thus the short-term administration of heparin did not alter the incidence or duration of ischemia in patients with unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1991

Exploration for physicians of the mature minor doctrine.

The "mature minor doctrine" is the common-law rule that allows an adolescent who is mature to give consent for medical care. Ethical decisions regarding consent and confidentiality should be distinguished from legal requirements. Recent court decisions have altered the law, especially in regard to consent for refusal of life-sustaining treatment. There are statutory exceptions to the rule of parental consent regarding emergency care, sexually transmitted diseases, drug treatment, mental health care, pregnancy, contraception, and emancipation. A detailed analysis of the mature minor exception is presented, utilizing court case vignettes. There is minimal legal risk in allowing adolescents older than 14 years of age to give consent for treatments entailing small degrees of risk, when they can make adultlike decisions and demonstrate signs of maturity.

Adolescent↗
PubMed1991

Effects of simulated extracorporeal circulation on human leukocyte elastase release, superoxide generation, and procoagulant activity.

Activated leukocytes are thought to contribute to respiratory dysfunction, alterations in microvascular permeability, disseminated intravascular coagulation, and thrombosis, all of which can complicate extracorporeal circulation. The purpose of this work was to determine the effects of extracorporeal circulation on leukocyte functions likely to mediate organ damage. White blood cell counts in the bubble circuits (n = 5) fell to 51% +/- 7% (mean +/- standard error of the mean; p less than 0.05) of initial levels within 2 hours of recirculation. In contrast, counts from both the spiral coil (n = 5) and hollow-fiber (n = 5) groups remained at 91% +/- 12% and 100%, respectively. Plasma levels of human neutrophil elastase rose from 0.28 +/- 0.06 micrograms/ml to 3.14 +/- 0.36 micrograms/ml (p less than 0.05) and 0.20 +/- 0.02 micrograms/ml to 1.61 +/- 0.35 micrograms/ml (p less than 0.05) in bubble and spiral coil circuits, respectively, but from only 0.20 +/- 0.03 micrograms/ml to 0.96 +/- 0.42 micrograms/ml in the hollow-fiber circuit despite 2 hours of recirculation. Consistently, in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine, a chemotactic peptide, cells from spiral coil and bubble circuits released and generated significantly less elastase and superoxide anion, respectively. In contrast, neutrophils from the hollow-fiber circuits demonstrated enhancement of N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced elastase release and superoxide generation. Finally, mixed leukocytes from all circuits expressed procoagulant activity reaching statistical significance in bubble circuits. In conclusion, extracorporeal circulation has pronounced effects on neutrophil elastase release, superoxide anion generation, and leukocyte procoagulant activity. Spiral coil and bubble oxygenators cause granule release and, subsequently, reduced sensitivity to soluble agonists. In contrast, hollow-fiber oxygenators "prime" cells, actually enhancing reactivity. Recirculation through all circuits induces leukocyte procoagulant activity that is likely to contribute to surface-induced thromboses and excessive bleeding.

Blood Coagulation↗
PubMed1990

Prevalence of maternal HIV infection based on unlinked anonymous testing of newborn babies.

This pilot study established that unlinked anonymous testing of dried blood spots routinely collected on Guthrie cards for neonatal screening is a feasible method for monitoring HIV prevalence in women at the time of delivery. The method was sensitive, specific, and less expensive than more conventional ELISAs. 114,515 dried blood spots taken from cards collected in three Thames regions were tested for antibody to HIV-1. 28 samples were confirmed to be antibody positive by western blot (seroprevalence 0.24 per 1000). Unlinked anonymous screening of newborn babies should be extended to monitor the spread of HIV infection in the heterosexual population and to target preventive strategies and provision of health care.

Agglutination Tests↗