Biomedical subjects

D Bigam

Publications and source records attributed to D Bigam.

4 recordsLinked to original sources

PubMed2001

The importance of impermeant support in small bowel preservation: a morphologic, metabolic and functional study.

BACKGROUND: Ambiguity exists as to which preservation solution is the most effective for small bowel (SB); studies have shown equivalent results with normal saline and University of Wisconsin (UW) solution. This study was designed to investigate the requirement of SB for oncotic and osmotic support, thereby reassessing one of the key principles of static organ storage. METHODS: Rodent SB was vascularly flushed with the following solutions: group 1, 0.9% saline (154 mM NaCl); group 2, 154 mM NaCl +5% dextran; group 3, 104 mM NaCl +100 mM lactobionate + 5% dextran; and group 4, UW solution. Analysis of cellular energetics, permeability and histology (by electron microscopy) was performed over a 10-h time course of cold storage. RESULTS: The addition of dextran and lactobionate to a simple saline solution (group 3) resulted in superior maintenance of several key parameters of energy metabolism throughout prolonged storage. At all times, ATP/ADP and EC ratios in group 3 remained unchanged from those of freshly isolated tissue; storage in normal saline and UW solution resulted in a progressive decline between 1 and 10 h of storage. ATP was also notably greater in group 3 than in group 1 or UW after 10 h of storage. Functional parameters demonstrated significant improvements in maintaining barrier function and membrane ion/electrical activity in group 3. Of particular note, after 10 h of storage, permeability for groups 1, 3 and UW was 215, 76 and 400 nmol/cm2/h, respectively, compared with a fresh tissue value of 22 nmol/cm2/h. Scanning electron micrographs revealed complete epithelial denudation of bowel stored in simple saline and UW solutions at 10 h. The incorporation of 100 mM lactobionate plus 5% dextran in group 3 prevented extensive villus denudation; the presence of intact microvilli indicated normal epithelial cell morphology. CONCLUSION: The order of solution effectiveness was group 3 > group 2 > group 1 > group 4. Vascular supplied impermeants, when supplied in simple solution, provide markedly improved preservation of metabolism, barrier function, and morphology of SB compared with UW.

Adenosine↗

PubMed2001

Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol.

Islet transplantation offers the prospect of good glycemic control without major surgical risks. After our initial report of successful islet transplantation, we now provide further data on 12 type 1 diabetic patients with brittle diabetes or problems with hypoglycemia previous to 1 November 2000. Details of metabolic control, acute complications associated with islet transplantation, and long-term complications related to immunosuppression therapy and diabetes were noted. Insulin secretion, both acute and over 30 min, was determined after intravenous glucose tolerance tests (IVGTTs). The median follow-up was 10.2 months (CI 6.5-17.4), and the longest was 20 months. Glucose control was stable, with pretransplant fasting and meal tolerance-stimulated glucose levels of 12.5+/-1.9 and 20.0+/-2.7 mmol/l, respectively, but decreased significantly, with posttransplant levels of 6.3+/-0.3 and 7.5+/-0.6 mmol/l, respectively (P < 0.006). All patients have sustained insulin production, as evidenced by the most current baseline C-peptide levels 0.66+/-0.06 nmol/l, increasing to 1.29+/-0.25 nmol/l 90 min after the meal-tolerance test. The mean HbA1c level decreased from 8.3+/-0.5% to the current level of 5.8+/-0.1% (P < 0.001). Presently, four patients have normal glucose tolerance, five have impaired glucose tolerance, and three have post-islet transplant diabetes (two of whom need oral hypoglycemic agents and low-dose insulin (<10 U/day). Three patients had a temporary increase in their liver-function tests. One patient had a thrombosis of a peripheral branch of the right portal vein, and two of the early patients had bleeding from the hepatic needle puncture site; but these technical problems were resolved. Two patients had transient vitreous hemorrhages. The two patients with elevated creatinine levels pretransplant had a significant increase in serum creatinine in the long term, although the mean serum creatinine of the group was unchanged. The cholesterol increased in five patients, and lipid-lowering therapy was required for three patients. No patient has developed cytomegalovirus infection or disease, posttransplant lymphoproliferative disorder, malignancies, or serious infection to date. None of the patients have been sensitized to donor antigen. In 11 of the 12 patients, insulin independence was achieved after 9,000 islet equivalents (IEs) per kilogram were transplanted. The acute insulin response and the insulin area under the curve (AUC) after IVGTT were consistently maintained over time. The insulin AUC from the IVGTT correlated to the number of islets transplanted, but more closely correlated when the cold ischemia time was taken into consideration (r = 0.83, P < 0.001). Islet transplantation has successfully corrected labile type 1 diabetes and problems with hypoglycemia, and our results show persistent insulin secretion. After a minimum of 9,000 IEs per kilogram are provided, insulin independence is usually attained. An elevation of creatinine appears to be a contraindication to this immunosuppressive regimen. For the subjects who had labile type 1 diabetes that was difficult to control, the risk-to-benefit ratio is in favor of islet transplantation.

Adult↗

PubMed1999

The hemodynamic effects of dobutamine infusion in the chronically instrumented newborn piglet.

OBJECTIVE: To determine the systemic, pulmonary, mesenteric, and renal hemodynamic effects of short and prolonged infusions of dobutamine. DESIGN: Prospective randomized unblinded study. SETTING: University research laboratory. SUBJECTS: Thirteen newborn (1-3 days old) piglets. INTERVENTIONS: Piglets were instrumented and studied 48 hrs later. Fifteen-minute infusions of dobutamine at 5, 10, 20 and 50 microg/ kg x min were randomly given with 15-min rests between the doses. After a 1-hr hiatus, a dose of 10 microg/kg x min was continuously administered for 2 hrs. MEASUREMENTS AND MAIN RESULTS: Systemic and pulmonary arterial pressures, cardiac index (thermodilution), and superior mesenteric and renal artery flows were measured. Vascular resistance values were calculated. MAIN RESULTS: Fifteen-minute infusions: Dobutamine dose-dependently increased cardiac index with tachycardia but not stroke volume (from 187 +/- 43 to 238 +/- 51 mL/kg x min at baseline and 50 microg/ kg x min, respectively, p < .05; values expressed as mean +/- SD). Systemic, but not pulmonary, vascular resistance decreased, resulting in a significant decrease in systemic to pulmonary arterial pressure ratio (from 3.8 +/- 0.8 at baseline to 3.2 +/- 1.0 at 50 microg/ kg x min). Superior mesenteric and renal flows were not affected. Two-hour infusion at 10 microg/kg x min: Cardiac index progressively increased from 173 +/- 34 to 240 +/- 58 mL/kg x min at baseline and 120 mins, respectively, (p < .05). The initial tachycardia was transient, and stroke volume was significantly increased at 60 mins and thereafter. Although systemic and pulmonary vascular resistance values fell simultaneously, systemic to pulmonary arterial pressure ratio decreased significantly to 3.4 +/- 0.9 at 120 mins from 3.9 +/- 0.7 at baseline. Superior mesenteric and renal artery flows increased significantly with vasodilation after 60 mins. CONCLUSIONS: Short infusions of dobutamine dose-dependently increase cardiac output due to tachycardia, without significant effect on mesenteric and renal blood flows. Prolonged infusion of dobutamine at 10 microg/kg x min progressively increases cardiac output and stroke volume with transient tachycardia, and increases mesenteric and renal blood flows. Caution is required in the treatment of critically ill neonates with dobutamine, which could also reduce systemic to pulmonary arterial pressure ratio.

Analysis of Variance↗

PubMed1999

Xenotransplantation.

As transplantation waiting lists lengthen because of the shortage of donor organs, the death rates of patients continue to rise. Xenotransplantation offers the potential to solve the problem of organ shortage br providing an unlimited supply of healthy donor organs. However, there are several barriers to xenotransplantation, including graft rejection, potential xenozoonosis, physiologic incompatibilities and ethical concerns. Experimental xenotransplantation studies continue in several areas, ranging from tissue to whole- organ grafting. Clinical studies continue in the area of tissue xenotransplantation. Trials with extracorporeal xenografts in an acute setting to support fulminant organ failure are likely to begin in the near future. The reintroduction of whole-organ xenotransplantation must be based on sound scientific analysis with broad societal input so as to offer the maximal benefit to transplant recipients and their families.

Animals↗