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Biomedical subjects

J Ryan

Publications and source records attributed to J Ryan.

At least 181 records · Page 10Linked to original sources
PubMed1991

Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: a Southwest Oncology Group study.

Disseminated soft-tissue sarcomas are a group of uncommon malignancies generally treated in a uniform manner. This study questioned the impact of schedule on response rate and toxicity in patients with metastatic soft-tissue sarcoma treated with the two-drug combination doxorubicin and dacarbazine. Patients were randomly assigned to receive either bolus therapy with doxorubicin at a dose of 60 mg/m2 and dacarbazine at a dose of 750 mg/m2 intravenously on day 1 (118 patients) or infusional therapy with doxorubicin at 60 mg/m2 and dacarbazine at 750 mg/m2 delivered by continuous intravenous infusion for 96 hours on days 1-4 (122 patients). Chemotherapy was to be repeated every 3 weeks. A unique feature of this cooperative group protocol was a provision for surgical resection of residual disease in patients with a partial response or with stable disease following chemotherapy. Similar overall response rates (17% in both treatment arms) and complete response rates (5% in both treatment arms) were observed. For patients receiving bolus therapy, the median response duration was 19.6 months for those in complete remission and 6.6 months for those in partial remission. For patients receiving infusional therapy, the median response duration was 12.6 months for those in complete remission and 9.3 months for those in partial remission. Examination of dose intensity received when combining treatment arms revealed a weak doxorubicin dose-response relationship. There was no difference in median survival times between the two treatment arms (bolus therapy, 10.6 months; infusional therapy, 10.5 months; logrank P = .97). Analysis of toxic effects favored infusional therapy. Significant reductions in cardiac toxicity (all events, P = .04; clinical events, P = .01) and nausea and emesis (P = .04) were seen in infusional therapy. Of 47 patients eligible for cytoreductive surgery following chemotherapy, 12 received surgery, and of those 12, eight were rendered disease free. The use of a 96-hour continuous intravenous infusion of doxorubicin-dacarbazine was comparable therapeutically with bolus dosing of these two agents and was better tolerated by the patients.

Adolescent↗
PubMed1991

Activation of the coagulation mechanism on tumor necrosis factor-stimulated cultured endothelial cells and their extracellular matrix. The role of flow and factor IX/IXa.

Infusion of tumor necrosis factor (TNF) into tumor-bearing mice led to intravascular clot formation with fibrin deposition in microvessels in the tumor bed in close association with the vessel wall, which could be prevented by active site-blocked factor IXa (IXai). This observation prompted us to examine the role of the intrinsic system in activation of the coagulation mechanism on TNF-stimulated human endothelial cell monolayers and endothelial-derived matrix during exposure to purified coagulation factors or flowing blood. Treatment of endothelial cells in intact monolayers with TNF induced expression of the procoagulant cofactor tissue factor (TF) in a dose-dependent manner, and after removal of the cells, TF was present in the matrix. TNF-treated endothelial cell monolayers exposed to blood anticoagulated with low molecular weight heparin induced activation of coagulation. Addition of IXai blocked the procoagulant response on TNF-treated endothelial cells, and consistent with this, the presence of factor IX/VIIIa enhanced endothelial TF/factor VII(a) factor X activation over a wide range of cytokine concentrations (0-600 pM). When TF-dependent factor X activation on endothelial cells was compared with preparations of subendothelium, the extracellular matrix was 10-20 times more effective. IXai blocked TF/factor VII(a) mediated activated coagulation on matrix, but only at lower concentration of TNF (less than 50 pM). Similarly, enhancement of factor Xa formation on matrix by factors IX/VIIIa was most evident at lower TNF concentrations. When anticoagulated whole blood flowing with a shear of 300 s-1 was exposed to matrices from TNF-treated endothelial cells, but not matrices from control cells, fibrinopeptide A (FPA) generation, fibrin deposition, and platelet aggregate formation were observed. FPA generation could be prevented by a blocking antibody to TF and by active site-blocked factor Xa (Xai) over a wide range of TNF concentrations (0-600 pM), whereas IXai only blocked FPA generation at lower TNF concentrations (less than 50 pM). Activation of coagulation on matrix from TNF-stimulated endothelial cells was dependent on the presence of platelets, indicating the important role of platelets in propagating the reactions leading to fibrin formation. These observations demonstrate the potential of cytokine-stimulated endothelium and their matrix to activate coagulation and suggest the importance of the intrinsic system in factor Xa formation on cellular surfaces.

Animals↗
PubMed1991

Augmentin-induced jaundice.

OBJECTIVE: To alert clinicians to the hepatotoxic potential of Augmentin (amoxycillin and clavulanic acid), a widely prescribed antibiotic, in susceptible patients, and to point out that the hepatic illness may be delayed but serious and protracted. DESIGN AND SETTING: Case reports of patients with Augmentin-induced jaundice referred to the gastroenterology departments in three major teaching hospitals, and a review of cases reported to the Australian Adverse Drug Reactions Advisory Committee (ADRAC). PATIENTS: Eight patients with nine episodes of Augmentin-induced jaundice personally treated by the authors from March 1988 to February 1990 are described. A further 19 patients reported to ADRAC from May 1987 to November 1989 are discussed. All patient histories were carefully reviewed to ensure that there was a temporal relationship between the course of Augmentin and the onset of the hepatitic illness and that other causes of jaundice were reasonably excluded. RESULTS: Jaundice developed in some of these patients several weeks after drug treatment was completed. The illness may be protracted over many weeks. As yet, there has been no case of progressive disease leading to the liver failure. CONCLUSIONS: The data suggest that a hypersensitivity reaction to clavulanic acid is the likely cause of the jaundice. Therefore, Augmentin, although an important antibiotic, should be reserved for severe infections for which amoxycillin is unsuitable.

Adult↗
PubMed1991

Workers' compensation cost shifting: an empirical study.

It has been suggested that health maintenance organizations (HMOs) overdiagnose work-related injuries and illnesses to increase their income. This study compared the Workers' Compensation experience of 2,176 Boston postal employees enrolled in a large HMO with that of 3,473 employees enrolled in a large fee-for-service health insurance plan. It controlled for the potential confounders of age, gender, job classification, type of injury, and duration of employment. It found no difference in the incidence of injuries: 5.93% for HMO enrollees and 6.25% for fee-for-service plan enrollees. Medical costs averaged $475 for HMO enrollees and $838 for fee-for-service plan enrollees (p = 0.018). Total costs averaged (09 for HMO enrollees and $1388 for fee-for-service plan enrollees (p = 0.063). In our cohort, there was no evidence of cost shifting. It appeared that the HMO provided less expensive medical care for injured postal workers.

Boston↗
PubMed1991

Risk and severity of non-back occupational injuries after lumbar laminectomy for degenerative disc disease.

An increased risk, after lumbar laminectomy, for lost work time occupational back injury (odds ratio, 5.9; 95% confidence interval, 1.9-18.8) and disability (mean 292.8 days vs. 24.8 for controls) was previously demonstrated. Such differences could be due to physical sequelae of back surgery or to psychosocial factors. Extensive literature addresses the impact of psychosocial factors on the incidence of occupational injury and severity of disability. This study assumes that psychosocial factors would affect both back and non-back injuries, while surgery-related physical factors would not. The odds ratio for non-back lost work time injury for subjects in the same cohort studied previously was 1.5 (0.5-4.5), with no significant increase in duration of disability (mean 27.0 days vs. 24.8 for controls). The increased risk for back injury in the absence of an increased risk for other injuries suggests that physiologic rather than psychosocial factors provide the more likely explanation for the differences in back injuries.

Adult↗
PubMed1991

A case-control study of risk factors for industrial low back injury: implications for primary and secondary prevention programs.

Data were collected on 228 consecutive back injuries in Boston's General Mail Facility and 228 non-injured controls drawn randomly from each case's work unit, matching on craft (clerk, mailhandler, maintenance), shift, and general supervisor. Data were collected on age, gender, duration of employment, 3 year history of injury claims, overtime work in the past 2 weeks, job change in the past 60 days, and machine vs. manual job. Risk factors for back injury were examined simultaneously in a conditional logistic regression for matched pairs. Risk factors included history of back injury claim (OR = 16.5, p less than 0.0001), younger age (OR = 3.0, p = 0.0001), shorter duration of employment (OR = 2.6, p = 0.0007), recent job change (OR = 2.5, p = 0.06), and history of non-back injury claim (OR = 2.0, p = 0.08). Among heavy lifters (vs. clerks) overtime and being female increased the risk of injury. In this setting, higher risk workers who may benefit from preventive education programs can be identified.

Accidents, Occupational↗
PubMed1991

Bioimpedance versus thermodilution cardiac output measurement: the Bomed NCCOM3 after coronary bypass surgery.

Values obtained for cardiac output (CO) were compared using thermodilution (TD) with those obtained using bioimpedance (Bi) as measured using the Bomed NCCOM3 (Revision 6) in 28 consecutive patients in the first 24 h after coronary artery bypass surgery (CABS). In 46 paired measurements made in the first 12 h after CABS Bi values for CO were significantly lower than TD values, the limits of agreement between the two methods were also unacceptably large (mean Bi 4.38 (SD 1.40) l/min, mean TD 5.46 (SD 1.19) l/min, limits of agreement -3.05 to +0.89). In 55 paired measurements made after 12 h (all in spontaneously breathing patients) there was no significant difference between the two methods and acceptable limits of agreement, mean Bi 5.69 (SD 1.2) l/min mean TD 5.6 (SD 1.2) l/min, limits of agreement -0.99 to +1.17). The significantly lower BiCO values obtained in the first 12 h after CABS show that BiCO measurement is not consistently reliable in the intensive care setting.

Bias↗
PubMed1991

Renal function following extracorporeal lithotripsy in children.

Although extracorporeal shockwave lithotripsy (ESWL) has revolutionised the management of urinary calculous disease, the long-term effects of ESWL on renal function are not known. This study of 18 children demonstrated a mild, statistically insignificant decrease of 15% in DTPA measured glomerular filtration rate following ESWL. In view of this, we recommend that pretherapy and posttherapy estimates of renal function be obtained in all patients undergoing ESWL. Long-term follow-up is necessary to further quantify the effects of ESWL on the developing kidney.

Adolescent↗
PubMed1991

Nursing-led group modalities in a psychiatric inpatient setting: a program evaluation.

This examination of group practice activities conducted by nurses in an inpatient setting combined retrospective examination of practices and concurrent analysis of what is actually done on the units. The most striking finding of this evaluation of institutional nursing-led or co-led group activities was the significant decline in the number of groups. Second, and a related finding, was the need to standardize the format for documenting group activities and outlining the scope and function of these groups. And finally, the need for concise evaluation criteria and measures to document the achievement of stated patient outcomes was very apparent.

Adolescent↗
PubMed1991

Why is the gracilis muscle relatively uninvolved in neuromuscular disorders?

CT scanning of thigh muscles has shown that the gracilis is often relatively resistant to degeneration in neuromuscular disorders. We have compared the histometric features of the gracilis muscle with the biceps femoris and vastus lateralis muscles in the right and left thighs of 12 subjects without neuromuscular disease. There was striking variation between individuals, but marked similarities between the two limbs in individuals. The gracilis and vastus lateralis muscles contained fewer Type 1 fibres than the biceps femoris. The Type 2 fibres were slightly larger in vastus lateralis than in the other two muscles. There is thus no evident morphological difference between the gracilis muscle and other thigh muscles that can be correlated with the different susceptibility of these muscles in neuromuscular diseases. However, these muscles are subject to differing physiological stresses in movement, and these may be important in determining the response to disease.

Female↗
PubMed1991

Evaluation of the in vitro production of tumour necrosis factor by monocytes in dialysis patients.

Modification of the cellular immune response in uraemia is partly responsible for the increased susceptibility to infection found in dialysis patients. In order to study this further we have evaluated the in vitro production of tumour necrosis factor (TNF) by peripheral-blood monocytes (PBMCs) to stimulation by lipopolysaccharide (LPS) from dialysis patients with end-stage renal failure. The patients were subdivided into two groups according to the type of dialysis: those undergoing haemodialysis (HD; n = 12) and continuous ambulatory peritoneal dialysis (CAPD; n = 18). Results were compared with those of controls taken from healthy laboratory staff (n = 7). The experiments show that the secretion of TNF by of TNF by PBMCs in response to LPS is significantly augmented in patients undergoing HD when compared to those on CAPD (81.3 +/- 38.7 vs. 18.2 +/- 13.3 U/ml, mean +/- SD, p less than 0.001) and controls (81.3 +/- 38.7 vs. 18.1 +/- 6.6 U/ml, p less than 0.001). There was no significant difference between the CAPD group and controls. In vitro production of TNF fell slightly following a single HD session (81.3 +/- 38.7 U/ml before HD and 50.5 +/- 28.7 U/ml after HD, p less than 0.05). We conclude from this study that TNF release from PBMCs is augmented in patients with chronic renal failure receiving chronic HD but not in a similar group receiving CAPD, in vitro. TNF release, however, is suppressed immediately following a single HD session. We suggest that HD rather than uraemia per se up-regulates monocyte secretion of TNF in vitro and that this is not an immediate response to activation by membrane polymer.

Adolescent↗
PubMed1991

Active site-blocked factor IXa prevents intravascular thrombus formation in the coronary vasculature without inhibiting extravascular coagulation in a canine thrombosis model.

To assess the contribution of Factor IX/IXa, to intravascular thrombosis, a canine coronary thrombosis model was studied. Thrombus formation was initiated by applying current to a needle in the circumflex coronary artery. When 50% occlusion of the vessel developed, the current was stopped and animals received an intravenous bolus of either saline, bovine glutamyl-glycyl-arginyl-Factor IXa (IXai), a competitive inhibitor of Factor IXa assembly into the intrinsic Factor X activation complex, bovine Factor IX, or heparin. Animals receiving saline or Factor IX developed coronary occlusion due to a fibrin/platelet thrombus in 70 +/- 11 min. In contrast, infusion of IXai prevented thrombus formation completely (greater than 180 min) at doses of 460 and 300 micrograms/kg, and partially blocked thrombus formation at 150 micrograms/kg. IXai attenuated the accumulation of 125I-fibrinogen/fibrin at the site of the thrombus by approximately 67% (P less than 0.001) and resulted in approximately 26% decrease in serotonin release from platelets in coronary sinus (P less than 0.05). Hemostatic variables in animals receiving IXai, remained within normal limits. Animals given heparin in a concentration sufficient to prevent occlusive thrombosis had markedly increased bleeding, whereas heparin levels that maintained extravascular hemostasis did not prevent intracoronary thrombosis. This suggests that Factor IX/IXa can contribute to thrombus formation, and that inhibition of IXa participation in the clotting mechanism blocks intravascular thrombosis without impairing extravascular hemostasis.

Animals↗
PubMed1991

Endothelium and regulation of coagulation.

Endothelial cells form the luminal vascular surface and thus have a central role in the regulation of coagulation. One important way in which endothelial cells control the clotting system is by regulating the expression of binding sites for anticoagulant and procoagulant factors on the cell surface. In the quiescent state, endothelial cells maintain blood fluidity by promoting the activity of numerous anticoagulant pathways, including the protein C/protein S pathway. After activation, as can be brought about by cytokines, the balance of endothelial properties can be tipped to favor clot formation through coordinated induction of procoagulant and suppression of anticoagulant mechanisms. Tumor necrosis factor suppresses the endothelial anticoagulant cofactor thrombomodulin and induces expression of the procoagulant cofactor tissue factor. Working in concert, these changes can allow fibrin formation to proceed in an inflamed focus but maintain blood fluidity in the surrounding area of normal vasculature. Recent studies suggest that similar changes in endothelial coagulant properties can be induced by advanced glycosylation end products, proteins modified by glucose that accumulate in the vasculature at a rapid rate in diabetic subjects, indicating the potential relevance of these mechanisms in diabetic vascular disease.

Animals↗
PubMed1991

Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma.

Between 1975 and 1989, 108 children with newly diagnosed medulloblastoma/primitive neuroectodermal tumor (MB/PNET) of the posterior fossa were treated at the authors' institution. The patients were managed uniformly, and treatment included aggressive surgical resections, postoperative staging evaluations for extent of disease, and craniospinal radiation therapy with a local boost. Beginning in 1983, children with MB/PNET were prospectively assigned to risk groups; those with "standard-risk" MB/PNET were treated with radiation therapy alone, while those in the "poor-risk" group received similar radiation therapy plus adjuvant chemotherapy with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), vincristine, and cisplatin. The 5-year actuarial disease-free survival rate for all patients treated between 1975 and 1982 was 68%, and 73% when patients who died within 2 weeks after operation were excluded. This survival rate was statistically better for patients treated after 1982 (82%) compared to those treated between 1975 and 1982 (49%) (p less than 0.004). There was no difference in disease-free survival rates over time for children with standard-risk factors; however, there was a significant difference in the 5-year survival rate for poor-risk patients treated prior to 1982 (35%) compared to those treated later (87%) (p less than 0.001). For the group as a whole, a younger age at diagnosis correlated with a poorer survival rate; however, this relationship between age and outcome was significant only for children treated before 1983 (p less than 0.001). These results demonstrated an encouraging survival rate for children with MB/PNET, especially those treated with aggressive surgical resection followed by both radiation therapy and chemotherapy. The results strongly suggest that chemotherapy has a role for some, and possibly all, children with MB/PNET.

Adolescent↗