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Biomedical subjects

J Malcolm

Publications and source records attributed to J Malcolm.

At least 19 recordsLinked to original sources
PubMed2005

Inhibition of p38 mitogen activated protein kinase controls airway inflammation in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) airways are characterised by chronic inflammation, increased interleukin (IL)-8 secretion, and neutrophil activation which are considered the principal factors of morbidity and mortality in CF patients. Optimising management of this chronic inflammatory response is therefore a key issue of basic and clinical CF research. Several reports have addressed ways to manage CF airways inflammation, and an attractive therapeutic strategy may be the inhibition of the p38-mitogen activated protein kinase (p38-MAP-k) pathway. METHODS: A new ex vivo model was used to study the mucosal inflammatory response to environmental airways stimuli. Nasal biopsy tissues from CF patients and controls were cultured ex vivo for 20 minutes, 4 hours, and 24 hours in the presence of lipopolysaccharide (LPS) from Pseudomonas aeruginosa (PA) with and without the p38-MAP-k inhibitor SB203580. Quantitative mRNA assessment, immunohistochemistry, and Western blots were used to detect the expression and modulation of inflammatory markers. RESULTS: PA-LPS challenge induced a time dependent mucosal inflammation indicated by rapid epithelial activation, IL-8 release, COX-2 upregulation, and neutrophil migration to the upper mucosal layers. Some of these LPS induced changes (IL-8 release and neutrophil migration) were specific to CF tissues. SB203580 significantly controlled all LPS induced mucosal changes in CF tissues. CONCLUSION: These findings provide a rationale and proof of principle for the potential use of p38-MAP-k inhibitors to control inflammation in patients with CF.

Adolescent↗
PubMed2005

Monosomy 7 associated with pediatric acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS): successful management by allogeneic hematopoietic stem cell transplant (HSCT).

Pediatric acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with monosomy 7 is associated with poor disease-free survival when treated by conventional chemotherapy, immunosuppression or supportive measures. Hematopoietic stem cell transplant (HSCT) may improve outcomes; however, data to support this are limited. To better understand the curative potential of HSCT in these patients, all cases of AML and MDS with monosomy 7 treated by two transplant programs (1992 to present) were reviewed. A total of 16 patients were treated, all by allogeneic HSCT. Primary diagnoses were MDS (N = 5), therapy-related MDS (N = 3), AML (N = 5) and therapy-related AML (N = 3). In all, 11 patients (69%) survive event-free at 2 years with median follow-up of 986 days (range 330-2011 days). Toxicity caused deaths of the five nonsurviving patients, four of whom were transplanted with active leukemia. Allogeneic HSCT is effective therapy for childhood AML and MDS associated with monosomy 7, particularly for patients with AML in complete remission and MDS.

Acute Disease↗
PubMed2000

Identification of risk factors for increased cost, charges, and length of stay for cardiac patients.

BACKGROUND: In this study we explored different risk model options to provide clinicians with predictions for resource utilization. The hypotheses were that predictors of mortality are not predictive of resource consumption, and that there is a correlation between cost estimates derived using a cost-to-charge ratio or a product-line costing approach. METHODS: From March 1992 to June 1995, 2,481 University of Colorado Hospital patients admitted for ischemic heart disease were classified by diagnosis-related group code as having undergone or experienced coronary bypass procedures (CBP), percutaneous cardiovascular procedures (PCVP), acute myocardial infarction (AMI), and other cardiac-related discharges (Other). For each diagnosis-related group, Cox proportional hazards models were developed to determine predictors of cost, charges, and length of stay. RESULTS: The diagnosis groups differed in the clinical factors that predicted resource use. As the two costing methods were highly correlated, either approach may be used to assess relative resource consumption provided costs are reconciled to audited financial statements. CONCLUSIONS: To develop valid prediction models for costs of care, the clinical risk factors that are traditionally used to predict risk-adjusted mortality may need to be expanded.

Aged↗
PubMed1998

The impact of psychosocial need and needs resolution on quality of life in patients with brain tumors.

The diagnosis of cancer of the central nervous system (CNS) is often the diagnosis of an incurable, progressive disease with devastating effects on the physical, psychosocial, and cognitive functioning of patients. Because many of the treatment options are noncurative in nature, issues related to quality and quantity of life become paramount. The purpose of the authors' research was to explore the prevalence of psychosocial needs in this cancer population and to determine whether these needs and their resolution impact on quality of life (QOL). Telephone interviews were conducted with 75 patients in whom primary CNS cancer was diagnosed and who were able to pass the Mini-Mental Health Status Examination. Analysis of results indicated that the majority of patients (97.3%) had at least one concern; concerns over treatment side effects, controlling uncertainty, having a meaningful existence, self and body image, and family concerns were among the five most frequently cited need domains. Most patients (91.8%) received help. However, 75.3% reported needing additional help. The number of needs reported and the severity of fatigue most significantly impacted QOL. The study identified the needs and experiences of the patient with CNS cancer. Quality of life and needs assessment information can be used to screen patients for distress and to measure the outcome of medical and psychosocial care and ultimately to ease the burden of illness.

Journal Article↗
PubMed1998

Grapefruit juice-drug interactions.

The novel finding that grapefruit juice can markedly augment oral drug bioavailability was based on an unexpected observation from an interaction study between the dihydropyridine calcium channel antagonist, felodipine, and ethanol in which grapefruit juice was used to mask the taste of the ethanol. Subsequent investigations showed that grapefruit juice acted by reducing presystemic felodipine metabolism through selective post-translational down regulation of cytochrome P450 3A4 (CYP3A4) expression in the intestinal wall. Since the duration of effect of grapefruit juice can last 24 h, repeated juice consumption can result in a cumulative increase in felodipine AUC and Cmax. The high variability of the magnitude of effect among individuals appeared dependent upon inherent differences in enteric CYP3A4 protein expression such that individuals with highest baseline CYP3A4 had the highest proportional increase. At least 20 other drugs have been assessed for an interaction with grapefruit juice. Medications with innately low oral bioavailability because of substantial presystemic metabolism mediated by CYP3A4 appear affected by grapefruit juice. Clinically relevant interactions seem likely for most dihydropyridines, terfenadine, saquinavir, cyclosporin, midazolam, triazolam and verapamil and may also occur with lovastatin, cisapride and astemizole. The importance of the interaction appears to be influenced by individual patient susceptibility, type and amount of grapefruit juice and administration-related factors. Although in vitro findings support the flavonoid, naringin, or the furanocoumarin, 6',7'-dihydroxybergamottin, as being active ingredients, a recent investigation indicated that neither of these substances made a major contribution to grapefruit juice-drug interactions in humans.

Administration, Oral↗
PubMed1997

Cost analysis of the introduction of PBPC for autologous transplantation: effect of switching from bone marrow (BM) to peripheral blood progenitor cells (PBPC).

Increasingly, PBPC instead of BM are used for autologous transplantation. Limited data exist on the economic effects of this change. Using a resource-based utilization model we prospectively determined the costs of 48 autologous transplants (eight BM, 17 BM + PBPC, 23 PBPC), isolating the post-reinfusion period (day 0 to discharge) to better determine the effect of the rescue product. Length of stay post-reinfusion was significantly shorter in patients receiving PBPC (median 13 days) or BM + PBPC (median 14 days) vs BM alone (median 20 days) (P < 0.01). Accordingly, transplant admission costs were less in the PBPC groups (PBPC $22089, BM + PBPC $23179) vs the BM alone group ($32289) (P < 0.05). Rescue product acquisition costs were higher for PBPC (range $3439-$5157) vs BM ($2766) but these costs were offset by the more rapid recovery of patients receiving PBPC. Overall transplant costs depend on the conditioning regimen with a 10-fold cost variation among regimens. Modeled costs for autologus transplantation using various approaches to rescue product acquisition are given. The introduction of PBPC for autologus transplantation has resulted in cost savings at our institution. Although the acquisition costs of PBPC rescue product are greater than for BM, this incremental expense is more than offset by a less expensive post-reinfusion period.

Adolescent↗
PubMed1992

Effects of feeding ponderosa pine needles during pregnancy: comparative studies with bison, cattle, goats, and sheep.

Four experiments were conducted to determine the effect of feeding dried pine needles (Pinus ponderosa; PN) on the abortion rate of ruminants. In Exp. 1, cattle were fed 5.4 kg of PN daily for 21 d starting at 116, 167, 215, or 254 d of pregnancy. The PN did not cause abortions when started at 116 d; thereafter, the percentage of cows that aborted increased linearly, and the interval to abortion decreased linearly (both P < .01); all cows fed PN beginning at 254 d aborted. In Exp. 2, cattle were fed .7, 1.4, or 2.7 kg of PN for 21 d or 2.7 kg for 1 or 3 d. Sheep and goats were fed .8 and .5 kg of PN, respectively, starting at 121 d of pregnancy. The PN induced some abortions in cattle when fed for 1 (11%) or 3 (30%) d, but the abortion rate was greater (P < .01) when the PN were fed for longer periods of time (80, 90, and 100% aborted in 19, 17, and 10 d for .7-, 1.4-, and 2.7-kg doses, respectively). No goats or sheep aborted in response to PN feeding. Pregnancy rates during the next breeding season for cows that aborted in response to the PN were slightly higher than rates for control cows (94 vs 87%). In Exp. 3, buffalo (Bison bison) and cattle were fed 2.25 kg of PN from the same collection. Abortions were induced in all buffalo and cattle that were fed PN.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Veterinary↗
PubMed1986

Salvage of ischaemic myocardium by reperfusion: importance of collateral blood flow and myocardial oxygen demand during occlusion.

Early reperfusion after coronary artery occlusion is used to treat acute myocardial infarction, but the factors that determine whether salvage of ischaemic myocardium actually occurs remain poorly defined. Differences in collateral blood flow to the region at risk, and haemodynamic variables during occlusion, may contribute to uncertainty as to the time beyond which reperfusion no longer reduces infarct size. To clarify this issue, open chest anaesthetised dogs underwent 1, 2, 3, 4, or 6 hours of left anterior descending coronary artery occlusion followed by reperfusion or permanent occlusion (n = 8 per group). Microspheres were injected before occlusion and 15 minutes after occlusion for regional myocardial blood flow determination, and heart rate and arterial blood pressure were measured before occlusion and 10 minutes and 30 minutes after occlusion. At 96 hours after occlusion haemodynamic variables were again measured; the animals were then killed, and occluded bed size was determined by in vitro dye perfusion. The area of necrosis was quantified from histological sections and expressed as a percentage of occluded bed size (AN/OB). If duration of occlusion is considered alone, reperfusion beyond two hours did not salvage ischaemic myocardium in this model. If the results for occlusion equal to and greater than two hours are combined, the mean area of necrosis (27(2)%) was significantly greater than that produced by one hour of occlusion followed by reperfusion (10(4)%). For the animals undergoing occlusion for two or more hours or permanent occlusion, collateral blood flow significantly influenced the area of necrosis. When epicardial flow during occlusion was high (greater than 0.30 ml X min-1 X g-1 tissue) 13 out of 14 dogs undergoing occlusion for two or more hours or permanent occlusion developed small (AN/OB less than 27%) infarcts (mean AN/OB 17(2)%). In contrast, when epicardial collateral flow was low (less than 0.30 ml X min-1 X g-1) 14 out of 23 animals had large (AN/OB greater than 27%) infarcts (mean AN/OB 34(3)%). For the 23 dogs in which epicardial flow was low, heart rate during occlusion significantly influenced infarct size: the 14 dogs that developed large infarcts (AN/OB greater than 27%) had a higher mean heart rate (152(6) beats X min-1) than the nine that developed small infarcts (AN/OB less than 27%) (130(5) beats X min-1; p less than 0.025). Thus reperfusion at one hour after occlusion salvaged ischaemic myocardium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1979

Competitive approach may ease problems in delivery system.

Experts believe that the absence of effective market forces in the health care field removes incentives for efficiency from both providers and consumers of health care/In today's climate, the authors say, it may be that competition, not regulation, may help solve our current problems.

Delivery of Health Care↗