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Biomedical subjects

M Jordan

Publications and source records attributed to M Jordan.

At least 73 records · Page 4Linked to original sources
PubMed1995

Combined simultaneous kidney/bone marrow transplantation.

On the basis of observations in patients with long-term (28-30 years) renal allograft survival, all of whom had evidence of systemic microchimerism, we began a program of combined simultaneous kidney/bone marrow transplantation. Between 12/14/92, and 10/31/94, 36 kidney transplant recipients received 3-5 x 10(8) unmodified bone marrow cells/kg; 6 patients also received pancreatic islets, and 7 patients also received a pancreas. The mean recipient age was 39.0 +/- 10.8 years, and the mean donor age was 31.8 +/- 16.1 years; the mean cold ischemia time was 23.0 +/- 9.1 hr. Twenty control patients received kidneys alone, mainly because of refusal by the donor family to consent to vertebral body recovery; 3 of these patients also received a pancreas. The mean recipient age was 47.9 +/- 11.7 years, and the mean donor age was 41.5 +/- 17.9 years; the mean cold ischemia time was 28.6 +/- 6.2 hr. All patients received tacrolimus-based therapy, without radiation, cytoreduction, or induction antilymphocyte preparations. Blood was drawn prior to and at regular intervals after transplantation for detection of chimerism and for immunologic studies. With a mean follow-up of 11.1 +/- 5.8 months, all 36 study patients are alive, and 33 (92%) have functioning allografts with a mean serum creatinine of 1.9 +/- 1.2 mg/dl and a BUN of 26 +/- 9 mg/dl. Graft vs. host disease was not seen in any patient. The incidence of rejection was 72%; 11% of the patients required OKT3 or ATG for steroid-resistant rejection. The incidence of CMV was 14%, and that of delayed graft function was 17%. A total of 18 (90%) control patients are alive, and 17 (85%) have functioning allografts, with a mean serum creatinine of 2.1 +/- 1.3 mg/dl, and a BUN of 30 +/- 13 mg/dl. The incidence of rejection was 60%, and 10% required OKT3 or ATG. CMV was seen in 15%, and delayed graft function in 20% (P = NS). In the study patients, chimerism was detected in the peripheral blood of 30 of 31 (97%) evaluable patients by either PCR or flow cytometry. In the control patients, chimerism was seen in 9 of 14 (64%) evaluable patients (P < .02). Decreasing donor-specific responsiveness was seen in 6/29 (21%) evaluable study, and 4/14 (29%) evaluable control patients (P = NS). We conclude that combined kidney/bone marrow transplantation is associated with acceptable patient and graft survival, augmentation of chimerism, and no change in the early events after transplantation.

Adolescent↗
PubMed1995

Neutralization of endogenous IL-6 suppresses induction of IL-1 receptor antagonist.

IL-1 is a potent cytokine that promotes host defense and inflammation. These processes may be modulated by an IL-1 receptor antagonist (IL-1Ra) that binds to and blocks IL-1 receptors. The objective of this study was to define the cellular origin and regulation of IL-1Ra production during bacterial infection. Oral infection of mice with Yersinia enterocolitica resulted in expression of IL-1Ra mRNA and synthesis of IL-1Ra in Peyer's patches (PP), the local site of infection, as well as in noninfected organs such as spleens. By immunostaining, recruited circulating neutrophils were identified to be the primary source of IL-1Ra in tissues. Only approximately 20% of the IL-1Ra-staining cells were accounted for by inflammatory macrophages. Strikingly, neutralization of IL-6 by anti-IL-6 antiserum caused a suppression of both IL-1Ra mRNA in PP and synthesis of IL-1Ra in circulating neutrophils. Confirmatory evidence that IL-6 participates in the generation of IL-1Ra was obtained when rIL-6 induced, and anti-IL-6 antiserum blocked, IL-1Ra expression in cultures of macrophage and polymorphonuclear leukocytes (PMN). These findings suggest that IL-6 induced induction of IL-1Ra may provide a negative feedback loop, facilitating resolution of the inflammatory response locally and presumably at remote sites of infection.

Animals↗
PubMed1995

How do smokers differ from nonsmokers in their response to thrombolysis? (the TIMI-4 trial)

Smokers with acute myocardial infarction appear to have a better outcome after thrombolysis than do nonsmokers. To identify factors that could contribute to this curious finding, we analyzed data from the Thrombolysis in Myocardial Infarction (TIMI-4) trial, in which 382 patients with acute myocardial infarction were randomized to tissue plasminogen activator, anistreplase, or both. Coronary angiography was performed 90 minutes and 18 to 36 hours after randomization, a myocardial perfusion scan was performed at 18 to 36 hours and before discharge, and a radionuclide ventriculogram was obtained before discharge. Angiographic and clinical outcome variables were determined in current smokers, ex-smokers, and nonsmokers, and regression analysis was used to correct for differences in baseline characteristics. The in-hospital mortality of current smokers was lower than that of ex-smokers and nonsmokers: 2.3% versus 5.2% versus 7.0%, respectively (p = 0.04 by paired comparison, current vs nonsmokers). Ninety minutes after randomization, the incidence of TIMI grade 3 flow was significantly higher in smokers than in ex-smokers and nonsmokers (55% vs 43% and 45%, p = 0.02); this difference was no longer observed at the second angiogram, nor did smokers differ from nonsmokers with respect to residual stenosis, thrombus grade, infarct size, ejection fraction, or recurrent ischemia. Because a strong inverse relation exists between TIMI grade 3 flow at 90 minutes and mortality, our findings suggest that the lower mortality of current smokers after thrombolytic therapy may be related to a higher incidence of early, complete reperfusion.

Double-Blind Method↗
PubMed1995

Thrombolytic Therapy for Acute Myocardial Infarction in Patients with Prior Coronary Bypass Surgery: Results from the Thrombolysis in Myocardial Infarction (TIMI) 4 Trial.

Little data exist on the value of intravenous thrombolysis for acute myocardial infarction in patients with previous coronary bypass surgery. The Thrombolysis In Myocardial Infarction (TIMI) 4 trial was a randomized study comparing tissue plasminogen activator, anistreplase, or a combination in patients with evolving myocardial infarction; patients with previous coronary bypass surgery were not excluded. Coronary angiography was performed 90 minutes and 18-36 hours after randomization, a myocardial perfusion scan was performed at 18-36 hours and predischarge, and a radionuclide ventriculogram was obtained predischarge. Angiographic and clinical outcome variables were determined in patients with and without a history of coronary bypass surgery. A total of 416 patients were randomized and 13 of them had previous bypass surgery; of these, 6 had an occluded vein graft as the infarct-related vessel. The incidence of TIMI grade 3 flow at 90 minutes was lower in patients with previous coronary surgery as compared with controls (42% vs. 49%), and overall patency was significantly lower (50% vs. 77%, p = 0.04). This trend persisted at 18-36 hours after randomization. Furthermore, patients with previous coronary surgery had more thrombus in their infarct-related arteries, especially with occlusion of a vein graft (83% vs. 32%, p = 0.04) and higher rates of recurrent ischemia (15% vs. 8%) and recurrent infarction (23% vs. 5%, p = 0.03) than controls. Thus, in patients with previous coronary bypass surgery intravenous thrombolysis yields results that are inferior to those achieved in patients without such a history and alternative methods of reperfusion should be considered.

Journal Article↗
PubMed1995

A double-blinded prospective evaluation of recombinant human erythropoietin in acutely burned patients.

OBJECTIVE: To evaluate the effects of recombinant human erythropoietin (r-HuEPO) in attempting to prevent anemia in acutely burned patients. DESIGN: Prospective double-blind randomized study of 40 patients. METHODS: Patients with burns from 25% to 65% total body surface were enrolled. r-HuEPO or a placebo was begun within 72 hours of admission. Cell blood count, reticulocyte counts, transfusion requirements, and blood loss were measured. Comparison was carried out by the unpaired t test. MAIN RESULTS: There was no statistically significant difference in hemoglobin, hematocrit, reticulocyte count, ferritin, serum iron, total iron blinding capacity, or transfusion requirements. In patients with burns from 25% to 35%, the reticulocyte counts were statistically significantly higher. CONCLUSION: In our work the administration of r-HuEPO in acutely burned patients did not prevent the development of postburn anemia or decrease transfusion requirements. Increased erythropoiesis in smaller burns (25% to 35%) was observed and may indicate a reason for further study.

Adolescent↗
PubMed1995

Comparison of antimicrobial susceptibility methods for detection of penicillin-resistant Streptococcus pneumoniae.

We sought to determine if commercially available susceptibility tests were accurate in detecting penicillin resistance and relative resistance in Streptococcus pneumoniae. We compared the reference MIC method with oxacillin disk screening and three commercial tests, E-test (AB Biodisk), JustOne (Radiometer America), and MicroScan Pos MIC Panel Type 6 (Baxter Diagnostics), with 80 selected clinical isolates. Thirty-three additional isolates were tested by the reference method and the E-test to further validate the latter method. Oxacillin screening was effective in detecting all penicillin-resistant and relatively resistant strains of S. pneumoniae. The MicroScan method was not effective in detecting penicillin resistance or relative resistance. The JustOne system classified only 6 (35%) of 17 resistant strains correctly, with 11 resistant strains classified as relatively resistant. The E-test correctly classified 30 (83%) of 36 resistant isolates, with 6 resistant isolates interpreted as relatively resistant. For determining penicillin MICs for S. pneumoniae, the E-test was the most accurate of the commercial systems that we studied.

Humans↗
PubMed1995

Attitudes to and use of baby walkers in Dublin.

OBJECTIVES: To identify the rate of baby walker use, parental attitudes, and associated injuries. DESIGN: Parents of babies attending clinics for developmental assessment were surveyed by self administered questionnaire about their use, attitudes, and history of injuries associated with walkers. SETTING: Dublin, Ireland. SUBJECTS: Parents of 158 babies. RESULTS: Fifty five per cent of the sample used a walker. The main reasons for doing so included babies' enjoyment of them and the fact that the walker was used for an older sibling. Although none of the users listed safety concerns as a reason to stop using the walker, non-users (45%) did so; 12.5% of the users had at least one walker related injury. CONCLUSIONS: Parents of babies who use a walker perceive them as beneficial. However these babies are placed at unnecessary risk. It behoves all health professionals and child carers to alert parents to these dangers and the sale of walkers should be reviewed.

Adult↗
PubMed1995

Sulfation pathway of thyroid hormone metabolism in selenium-deficient male rats.

Male Sprague-Dawley rats were fed a selenium-deficient yeast-based laboratory diet or a control diet for 6 wk. The tissue type I 5'-monodeiodinase (5'-MDI) activity and the immunoassayable 5'-MDI were significantly (P < 0.05) reduced in the liver and the kidney but not in the thyroid of selenium-deficient rats. The mean serum concentrations of thyroxine sulfate (T4S), 3,3',5'-triiodothyronine sulfate (T3S), and reverse T3 sulfate (rT3S) (ng/dl) were significantly increased in selenium-deficient rats (15.7, 59.4, and 22.8, respectively, n = 12) compared with control rats (< 1.0, 18.5, and 9.1, respectively, n = 12, P < 0.01). Kinetic studies were carried out during a constant infusion of unlabeled sulfated iodothyronines (T4S, T3S, or rT3S, n = 5-6/group) at a rate of 1 microgram/h by Alzet minipump for 48 h. The data showed that elevated serum concentrations of T4S or T3S in the selenium-deficient rat are due both to reduced metabolic clearance rate (MCR, mean, l.kg-1.day-1, 7.4 for T4S and 4.5 for T3S in selenium deficiency vs. 12 and 9.2, respectively in controls, P < 0.05) and increased production rate (mean, microgram.kg-1.day-1, 1.2 for T4S, and 2.7 for T3S in selenium deficiency vs. 0.12 and 1.7, respectively, in the controls, P < 0.05). However, the increased serum rT3S concentration in selenium-deficient rats is due mainly to reduced MCR (mean, l.kg-1.day-1, 34 vs. 67 in controls, P < 0.05) and its daily production rate remained unchanged in selenium deficiency (mean, microgram.kg-1.day-1, 7.6 vs. 6.1 in the control group, P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Peroxidative stress in diabetic blood vessels. Reversal by pancreatic islet transplantation.

Diabetic complications are believed to arise, in part, through an increase in oxidative stress. We characterized antioxidant status in vascular tissue in untreated diabetic rats and in diabetic rats rendered euglycemic by pancreatic islet transplantation. Three key endogenous antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) were measured. Sprague-Dawley rats with streptozotocin-induced diabetes were killed after 8 weeks of untreated hyperglycemia and compared with age-matched controls. Eight weeks of untreated diabetes resulted in a significant increase of tissue catalase in aorta, iliac artery, and femoral artery as compared with controls. No significant changes in either superoxide dismutase or glutathione peroxidase were observed in aorta, iliac artery, or femoral artery of diabetic animals. This increase in catalase in diabetic vascular tissue suggests increased oxidative stress due to chronic exposure to H2O2 in vivo. To assess the impact of islet transplantation on oxidative stress in vascular tissue, inbred Lewis strain rats were rendered diabetic with streptozotocin. After 8 weeks of untreated diabetes, rats received an intraportal islet isograft and were monitored for 4 subsequent weeks of euglycemia. Islet transplantation improved weight gain and normalized blood glucose and total glycosylated hemoglobin. While catalase was significantly increased in aorta and iliac artery at 8 and 12 weeks of diabetes, vascular catalase was restored to normal by islet transplantation. These data suggest that islet transplantation is an effective treatment strategy to minimize increased oxidative stress in diabetic vasculature.

Animals↗
PubMed1995

Syngeneic pancreatic islet transplantation reverses endothelial dysfunction in experimental diabetes.

Diabetes is known to cause impaired endothelium-dependent relaxation of blood vessels. The purpose of this study was to determine whether this endothelial dysfunction is a permanent defect or is reversible after acute arginine supplementation in vitro or by surgical intervention in vivo using syngeneic pancreatic islet transplantation. Lewis rats were injected with streptozotocin to induce diabetes and were studied either 8 or 12 weeks later. Another group received syngeneic islets via intraportal injection at 8 weeks of diabetes and were allowed to become euglycemic for 4 weeks before study. Thoracic aortic rings were tethered in isolated muscle baths, contracted with a submaximal concentration of norepinephrine, and challenged with either the endothelium-dependent vasodilator acetylcholine or the endothelium-independent vasodilator nitroglycerin. Relaxation to acetylcholine (but not nitroglycerin) was reduced in both 8- and 12-week diabetic rings compared with age-matched control rings. Preincubation of diabetic rings in vitro with L-arginine (but not D-arginine) restored relaxation to acetylcholine to normal to rings from 8-week but not 12-week diabetic animals. Plasma basic amino acids (arginine, lysine, and histidine) were reduced by diabetes, whereas other neutral or acidic amino acids were unchanged (phenylalanine, proline, and glutamate), reduced (serine, cysteine, threonine, tyrosine, tryptophan, and aspartate), or elevated (isoleucine, leucine, and valine). Islet transplantation restored to normal the changes in plasma amino acids. Elevation in blood glucose and total glycosylated hemoglobin in diabetic animals was normalized after islet transplantation. Furthermore, islet transplantation completely restored the defective endothelium-dependent relaxation to acetylcholine in diabetic rings.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗