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Biomedical subjects

J G O'Brien

Publications and source records attributed to J G O'Brien.

At least 19 recordsLinked to original sources
PubMed2000

Effects of tranexamic acid and aprotinin, two antifibrinolytic drugs, on PAF-induced plasma extravasation in unanesthetized rats.

Two antifibrinolytic drugs, tranexamic acid (TXA), and aprotinin (APR), are currently used to improve the recovery of patients following major surgery while reducing blood loss. Their mechanisms of action have yet to be fully understood. Here, we examined (1) the effects of TXA or APR on basal vascular permeability (VP) and (2) the effects of TXA or APR on platelet-activating factor (PAF)-induced increase of VP in normal unanesthetized rats. Evans blue dye (EB) bound to albumin was used as the marker of extravasation in selected tissues. In normal rats, PAF (1 microg/kg i.v.) increased VP in most selected tissues including bronchi, aorta, duodenum and pancreas without affecting blood pressure. TXA (up to 300 mg/kg i.v.) had no significant effect on basal VP in any tissues, while APR (30000 KIU/kg i.v.) decreased basal VP in 5 out of 8 tissues. Pre-treatment with TXA decreased PAF-induced increases of VP in the microcirculation of the thoracic and abdominal aorta, the duodenum and the pancreas, from 35% to 41%. TXA was mostly effective at an i.v. dose of 100 mg/kg with a 2 h of pre-treatment period. Pre-treatment with APR also reduced PAF-induced increases of VP in selected tissues by 35 to 61%. The i.v. dose of 30000 KIU/mg was optimal when injected at least 30 min before the administration of PAF + Evans blue. These results suggest that the beneficial effect of APR and TXA, following cardiopulmonary bypass (CPB) and other type of surgeries, may be attributed to the inhibition of plasma exudation mediated, at least in part, by PAF. Thus, TXA and APR may improve patients recovery by reducing the capillary leakage of albumin, associated with interstitial edema formation, and maintaining intravascular fluid volume.

Animals↗
PubMed1997

A 5-year retrospective review of adverse drug reactions and their risk factors in human immunodeficiency virus-infected patients who were receiving intravenous pentamidine therapy for Pneumocystis carinii pneumonia.

The incidence and severity of adverse drug reactions (ADRs) in human immunodeficiency virus-infected persons receiving intravenous pentamidine for Pneumocystis carinii pneumonia during a 5-year period were reviewed retrospectively. Predisposing risk factors for ADRs were identified. ADRs were included if they occurred during or within 1 week following the discontinuation of pentamidine treatment. Nephrotoxicity, dysglycemia, hepatotoxicity, hyperkalemia, and hyperamylasemia accounted for 80% of ADRs (n = 174) that occurred in 76 (71.7%) of 106 patients during 84 treatment courses of pentamidine. A significant relationship between hypoglycemia and nephrotoxicity was observed (P = .002). Four factors were significantly associated with occurrence of an ADR: number of concomitant medications (odds ratio [OR] = 1.36, P = .005), nonwhite ethnicity (OR = 5.00, P = .017), cumulative dosage of pentamidine (OR = 1.03, P = .030), and concurrent use of other nephrotoxic drugs (OR = 2.34, P = .047). Two factors, daily dosage and history of intravenous drug use, approached significance. Knowledge of and avoidance of potential risk factors might allow safer use of pentamidine and reduce the prevalence of ADRs.

AIDS-Related Opportunistic Infections↗
PubMed1997

Aprotinin, an antifibrinolytic drug, attenuates bradykinin-induced permeability in conscious rats via platelets and neutrophils.

Two antifibrinolytic drugs, tranexamic acid (TXA) and aprotinin (APR), are used to improve the recovery of patients following cardiac surgery while reducing blood loss. Their mechanisms of action have yet to be fully understood. To investigate their possible mechanisms of action during cardiopulmonary bypass, we examined (i) the effects of TXA and APR on bradykinin (BK) induced vascular permeability (VP) in conscious rats, (ii) the roles of platelets and neutrophils in this reaction, and (iii) the effects of TXA or APR on BK responses in platelet- or neutrophil-depleted rats. Evans blue dye (EB) was used as the marker of extravasation. The animals were treated with antiplatelet serum for platelet depletion or with methotrexate for neutrophil depletion. In normal rats, BK increased VP in most tissues. Thrombocytopenia and neutropenia also increased basal VP. TXA had no significant effect whereas APR decreased basal VP. In the second series of experiments, APR significantly attenuated BK-induced increases in VP, whereas TXA was completely ineffective. Platelet depletion did not affect BK-induced increases of VP, except for a massive plasma exudation in the lung parenchyma. Neutrophil depletion also had no effect on BK-induced increases of VP, except for an attenuation in the duodenum. In the third and last series of experiments, TXA potentiated the effect of BK in the upper and lower bronchi of platelet-depleted rats, compared with the effects of TXA on BK in normal animals, except in the lung parenchyma, where TXA blocked the increase of VP induced by BK. APR also potentiated the effect of BK in the lower bronchi of platelet-depleted rats. Overall, the inhibitory effect of APR on the VP induced by BK in normal rats was attenuated in platelet-depleted rats. Like TXA, APR blocked the increase of VP induced by BK in the lung parenchyma of platelet-depleted rats. In neutrophil-depleted rats, TXA did not affect the permeabilizing response to BK. In those rats, the inhibitory effect of APR against BK increases of VP was attenuated. These results show that the beneficial effect of APR, but not TXA, following cardiac surgery may be attributed to the inhibition of plasma exudation mediated, in part, by BK. In addition, platelets and neutrophils do not appear to be involved in BK-mediated plasma exudation. However, both cell types are essential for the regulation of basal VP. Finally, the mechanism underlying the protective inhibitory effect of APR on BK-induced increases of VP involves, at least in part, platelets and neutrophils, since the inhibitory effect of APR is attenuated in thrombocytopenic and neutropenic rats. Both cell types are not involved in the action of TXA on VP. Therefore, maintaining platelet and neutrophil counts following cardiopulmonary bypass could enhance the protective effect of APR.

Animals↗
PubMed1996

Lithium and angiotensin-converting enzyme inhibitors: evaluation of a potential interaction.

The potential interaction between lithium and angiotensin-converting enzyme (ACE) inhibitors was investigated in a retrospective, longitudinal, case-control study of 20 hypertensive patients previously stabilized on lithium therapy. The objective of the study was to determine the impact of ACE inhibition on steady-state lithium concentrations and to evaluate the potential association of altered lithium clearance with age, renal function, and electrolyte balance. After initiation of the ACE inhibitor, steady-state lithium concentrations increased by 36.1%, lithium clearance was reduced by 25.5% (p < 0.0001), and four patients presented with symptoms suggestive of lithium toxicity. Significant bivariate correlations were observed for lithium clearance change and age (r = -0.45; p < 0.05) and for lithium clearance change and serum creatinine (r = -0.52; p < 0.02). Multiple regression analysis indicated that 25% of the change in lithium clearance was associated with a change in serum creatinine. This percentage was increased to 35% by the inclusion of age in the regression model. None of the other variables (age, height, weight, or change in serum sodium/potassium) made a significant contribution to this model. The authors concluded that a clinically important increase in lithium concentrations can occur in patients started on ACE inhibitor therapy. As elderly patients may be uniquely predisposed to this interaction, avoidance of this medication combination in older populations should be considered.

Aging↗
PubMed1995

Effects of reinforcing increases in active behavior versus decreases in sedentary behavior for obese children.

This experiment tested the effects of reinforcing obese children lo be more active or less sedentary in their choice of active versus sedentary behaviors. On days I and 5, there were no contingencies for sedentary or active behaviors. During days 2 through 4, children in the Activity group were reinforced for being more active, and they significantly increased their activity and decreased time spent on preferred sedentary activities. Children in the Sedentary group were reinforced for not engaging in preferred sedentary behaviors, and they significantly decreased time spent on these sedentary behaviors, with lime reallocated both to being more active and to substitution of lower preference sedentary behaviors. Children randomized to the Control group were reinforced for attendance and made choices among the alternatives as usual, allocating most or their time during all 5 days for their preferred sedentary behaviors. These laboratory results support the idea that activity can be increased by either reinforcing children for being more active or for reducing lime spent in sedentary activities.

Journal Article↗
PubMed1994

Genetic analysis of liver tumorigenesis in SV40 T antigen transgenic mice implies a role for imprinted genes.

Liver tumors from interspecific hybrid, transgenic mice containing the SV40 early region linked to a mouse major urinary protein enhancer/promoter were analyzed for loss of heterozygosity to identify chromosomal regions which potentially contain genetic loci involved in multistep tumorigenesis. A broad pattern of complete and partial loss of heterozygosity or allelic imbalance was observed with frequent loss of heterozygosity/partial loss of heterozygosity of loci on chromosomes 1, 5, 7, 8, and 12. In tumors from Mus domesticus x Mus spretus F1 mice a strong preference for loss of the domesticus allele of H19 on chromosome 7 was observed, whereas loss of heterozygosity/partial loss of heterozygosity on chromosome 8 involved preferential loss of spretus alleles. In tumors from reciprocal crosses with Mus castaneus, the maternal chromosome 7 H19 allele was preferentially lost irrespective of whether it was domesticus or castaneus, strongly suggesting the involvement of an imprinted gene(s) in tumor progression.

Alleles↗
PubMed1994

Chromosome 8 alterations accompany tumorigenesis in renin-SV40 T antigen transgenic mice.

s.c. and abdominal tumors from interspecific hybrid, transgenic mice containing the SV40 early region linked to a renin enhancer/promoter were analyzed for loss of heterozygosity to identify chromosomal regions involved in tumorigenesis. A very high frequency of loss of heterozygosity/partial loss of heterozygosity or allelic imbalance involving the distal regions of chromosome 8 was observed in the s.c. tumors (76%) with frequent amplification (3-6 times) of the corresponding proximal regions including Junb, suggesting that chromosome 8 breakage and amplification promotes tumorigenesis in these mice.

Animals↗
PubMed1993

Diagnostic and treatment guidelines on elder abuse and neglect.

It is estimated that between 1.5 and 2 million older adults experience abuse or neglect each year in the United States. Elder mistreatment may be physical, psychological, or financial, and it may be perpetrated by family members or by other informal or formal caregivers. Physicians are encouraged to play an active role in assessment, intervention, and prevention.

Aged↗
PubMed1992

Acute pain in the elderly.

Acute-pain syndromes are common in the elderly. They often occur in association with the degenerative diseases that are likely to affect this age-group. Diagnosis of the specific type of acute pain is made difficult by several factors, including atypical presentation and underreporting. Treatment can be complicated by the polypharmacy that is prevalent among older adults and by age-related physiologic changes. Effective management requires knowledge of the effects of various pharmacologic agents in older adults and of the health and psychosocial status of the individual patient.

Acute Disease↗
PubMed1989

Evaluation of acute confusion (delirium).

Acute confusion in the elderly is a problem that has high prevalence with significant morbidity and mortality, and that may lead to institutional placement. It is imperative that delirium be recognized promptly and its underlying cause(s) identified and treated. Management requires a multifaceted approach that addresses the precipitating cause(s), maintenance and support of vital functions, management of behaviors with use of nursing staff and family, attention to the environment, and sometimes the use of appropriate psychotropic medication. Prompt treatment is likely to result in a return to normalcy.

Acute Disease↗
PubMed1987

'Healthy' prescribing for the elderly. How to minimize adverse drug effects and prevent 'dementia in a bottle'.

Despite constituting only 11% to 12% of the US population, the elderly use 31% of all prescription and over-the-counter drugs and, unfortunately, are most vulnerable to the adverse effects of drug therapy. Because of age-related physiologic changes and the likelihood of intercurrent disease, elderly patients need individualized prescribing. This requires the practitioner to be familiar with a few drugs in each class that are tolerated by and effective in elderly patients and to adhere to the principles of healthy prescribing, which have application in any setting. In conclusion, the words of Paracelsus (1493-1541) are worth recalling: "All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy."

Aged↗