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F R Bentley

Publications and source records attributed to F R Bentley.

At least 19 recordsLinked to original sources
PubMed2005

Ethical considerations in the early composite tissue allograft experience: a review of the Louisville Ethics Program.

This paper reviews the formulation and evolution of the ethical component in one of the earliest clinical composite tissue allograft (CTA) programs, the hand transplantation program in Louisville, Kentucky, USA. The purpose was to derive lessons and define principles to give guidance for future programs and introduction of new CTA. We reviewed the initial ethical considerations, including input from respected ethical scholars, guidelines for innovative procedures transparency in public and professional scrutiny, and compliance with human studies regulations (IRB approval). We found the initial focus on ethics, scholarly input, guidelines for innovative procedures, and human studies protection regulations to be valid. Moreover, we noted the effect of autonomy in subjective, quality-of-life benefits on equipoise and effective risk-benefit analysis in effective informed consent. We found that psychiatric screening and support to be exceptionally valuable in protecting autonomy, suitability for participation, assessing personality organization, and determining compliance ability. We conclude that the program ethical principles were validated. For future CTA programs and procedures, we recommend an ethical emphasis with adherence to high standards and transpire to independence to scrutiny and oversight. We recommend protection of autonomy judgments in equipoise judgment and informed consent. We recommend skilled psychiatric screening and support. We endorse scholarship, scientific accuracy, and data sharing.

Humans↗
PubMed1997

Lazaroids prevent acute cyclosporine-induced renal vasoconstriction.

BACKGROUND: Cyclosporine (CsA)-induced nephrotoxicity may be due to intrarenal vasoconstriction and glomerular hypoperfusion. Several factors, including endothelin and prostanoids, are suggested mediators of this response. Recent evidence suggests that CsA leads to increased oxygen-derived free radical (ODFR) production and lipid peroxidation in renal tissue. Whether this leads to alterations in renal vessel reactivity is unclear. Lazaroids, such as U74389G, are radical-quenching antioxidants that inhibit ODFR-induced lipid peroxidation and may improve renal function after ischemia and reperfusion. We hypothesized that ODFRs contribute to CsA-induced alterations of the renal microcirculation. METHODS: Rat hydronephrotic kidneys were studied by video microscopy. Interlobular arteriolar diameter and flow, afferent and efferent arteriolar diameters, and cardiac output were measured at 15-min intervals for 120 min. U74389G or its vehicle was infused 15 min before topical application of CsA to the kidney. The results were compared with U74389G alone and normal saline. RESULTS: CsA administration caused renal microvascular vasoconstriction (10-25% below baseline) and hypoperfusion (35% below baseline). Both vasoconstriction and hypoperfusion were significantly attenuated by U74389G (5-8% and 20% below baseline, respectively). CONCLUSIONS: Inhibition of lipid peroxidation by U74389G maintained renal blood flow during acute CsA administration. These data suggest that ODFRs are involved in the renal microvascular response to CsA. Inhibition of ODFR-induced lipid peroxidation may help prevent CsA-induced glomerular hypoperfusion. Lazaroids may prove an effective adjunct in reducing CsA-induced nephrotoxicity.

Animals↗
PubMed1997

Lazaroid improves intestinal blood flow in the rat during hyperdynamic bacteraemia.

BACKGROUND: Intestinal mucosal hypoperfusion and loss of barrier function during sepsis may contribute to maintaining the septic state. Free radicals are produced during sepsis and antioxidants improve survival from experimental sepsis. It is unclear whether endothelial cell injury from free radicals results in altered microvascular reactivity. Lazaroids are antioxidants which scavenge radicals and block lipid radical chain reactions. The authors sought to determine whether lazaroids altered the intestinal microvascular responses to sepsis. METHODS: In vivo video microscopy was used to study the ileal microcirculation of the rat. A1 (inflow) arteriolar diameter and flow, A3 (premucosal) arteriolar diameters, and cardiac output were measured. Lazaroid or vehicle was infused before a bolus injection of live Escherichia coli or saline. RESULTS: Lazaroid alone had no effect on the intestinal vessels or haemodynamics. E. coli caused vasoconstriction (A1, -21 per cent, A3, -19 per cent of baseline) and hypoperfusion (-36 per cent) despite increased cardiac output (+31 per cent). Lazaroid significantly attenuated both constriction (A1, -11 per cent; A3, 10 to -1 per cent) and hypoperfusion (-15 per cent), but did not increase cardiac output (30 per cent). CONCLUSION: E. coli bacteraemia led to intestinal vasoconstriction and hypoperfusion. Lazaroid reduced this effect without altering central haemodynamic responses, suggesting that free radicals have a deleterious effect on the intestinal microcirculation during bacteraemia.

Animals↗
PubMed1996

Vasomotor response to pentoxifylline mediates improved renal blood flow to bacteremia.

Bacteremia leads to rapid intrarenal vasoconstriction, mediated by endogenous vasoconstrictors such as TXA2 and endothelin. These changes occur before the onset of neutrophil adherence, platelet aggregation, or increases in proinflammatory cytokines. Pentoxifylline (PTX) increases red cell deformability, reduces neutrophil adhesion, abrogates rises in TNFalpha, and lessens the deleterious effects of other cytokines during prolonged sepsis. PTX also improves renal function in models of established sepsis, but the specific mechanisms of this effect are unclear. Because PTX is a relatively selective visceral vasodilator we sought to determine whether PTX improves renal microvascular hypoperfusion during bacteremia and whether the mechanism involves altered vascular reactivity. Rat hydronephrotic kidneys were studied by videomicroscopy. Interlobular (ILA) arteriolar diameter and flow, afferent (AFF) and efferent (EFF) arteriolar diameters, and cardiac output (CO) were measured at 15-min intervals for 120 min. PTX was infused alone or prior to a bolus injection of live Escherichia coli. The responses were compared to controls infused with equivalent volumes of normal saline alone. PTX led to improved renal blood flow and to pre- and postglomerular vasodilatation. This improvement remained significant compared to bacteremic animals throughout the period of observation. We conclude that PTX improves renal blood flow during bacteremia due to pre- and postglomerular vasodilation. These responses may be a consequence of increased intracellular cAMP and release of vasodilator prostanoids.

Animals↗
PubMed1996

Free radical scavenging by lazaroids improves renal blood flow during sepsis.

BACKGROUND: Acute kidney failure in surgical patients is often related to severe infection. Renal vasoconstriction is a major factor in the genesis of kidney failure. Reactive oxygen species (ROS) are known to mediate kidney injury after ischemia-reperfusion and are increased during sepsis. The role of ROS as mediators of intrarenal vasoconstriction and renal dysfunction during sepsis is unclear. Lazaroids such as U74389G are radical quenching antioxidants that inhibit ROS-induced lipid peroxidation. We sought to determine whether radical scavenging affected the renal microvascular response to a septic challenge. METHODS: In vivo videomicroscopy was used to study the rat hydronephrotic kidney. Interlobular artery (ILA) diameter and flow, afferent and efferent arteriolar diameters, and cardiac output were measured. U74389G or vehicle was infused before a bolus injection of live Escherichia coli or normal saline solution. RESULTS: U74389G alone had no effect on the renal vessels or hemodynamics. E. coli caused preglomerular vasoconstriction (ILA, -32%; afferent, -30% of baseline) and hypoperfusion (-66%) despite increased cardiac output (+54%). U74389G significantly attenuated both the constriction (ILA, -16%; afferent, -9%) and hypoperfusion (-38%) but not increased cardiac output (+41%). CONCLUSIONS: E. coli bacteremia led to preglomerular vasoconstriction and hypoperfusion. Inhibition of lipid peroxidation with the radical scavenger U74389G reduced this effect without altering central hemodynamic responses. Free radicals have a deleterious effect on the renal microcirculation during bacteremia, and these data suggest that antioxidants may be of value in preventing sepsis-associated kidney failure.

Animals↗
PubMed1996

Success and complications of pancreatic transplantation at one institution.

OBJECTIVE: The authors report the results and complications of the first 59 pancreas transplantation procedures performed at one institution. SUMMARY BACKGROUND DATA: Pancreas transplantation is performed at relatively few centers. Results have improved in the past few years. METHODS: A retrospective review was completed of the results and complications after pancreas transplantation at one institution. Pancreas transplantation was indicated for patients with insulin-dependent diabetes mellitus and who were younger than 50 years of age. The results were divided into era I (March 1987-December 1992) and era II (January 1993-October 1995). RESULTS: Fifty-nine transplants were performed since March 1987. There were 45 combined kidney/pancreas transplants and 13 pancreas transplants. Graft survival at 1 year was 57% for those in era I versus 79% in era II. Rejection occurred in 74% of the patients in era I and 48% in era II. Eighty-five percent of all rejection episodes in both eras were steroid resistant and required antibody therapy. Complications were not different from eras I and II. CONCLUSIONS: Pancreas transplantation is a successful procedure with a number of significant complications. Rejection episodes are most often steroid resistant.

Adult↗
PubMed1996

Type II diabetes after combined kidney and pancreas transplantation for type I diabetes mellitus and end-stage renal disease.

We report a case of a patient who developed type II diabetes after receiving a successful combined kidney and pancreas transplant for type I diabetes and end-stage renal disease. This patient underwent a combined kidney and pancreas transplant and had no evidence of rejection with good function following the transplant for nine months. The patient developed significant post-transplant obesity with her transplant weight of 80 kg rising to 109 kg. At this level of obesity, the patient developed fasting hyperglycemia of 180 mg/dl with no change in her renal function or her pancreas exocrine function. She developed hyperinsulinemia to this fasting hyperglycemia. The clinical course of this patient demonstrates that rapid weight gain following transplantation can result in type II diabetes.

Diabetes Mellitus, Type 1↗
PubMed1995

An experimental study of altered nitric oxide metabolism as a mechanism of cyclosporin-induced renal vasoconstriction.

Nephrotoxicity caused by cyclosporin A (CSA) is the result of vasoconstriction of the renal microcirculation. The endothelium-derived relaxing factor nitric oxide (NO) regulates microvascular blood flow in various tissues, and mediates the microcirculatory response during hypertension and sepsis. This study investigated the role of NO in CSA-induced renal vasoconstriction. Hydronephrotic kidneys in rats were suspended in an environmentally controlled tissue bath, and interlobular, afferent and efferent arteriolar diameters and blood flow were measured by in vivo videomicroscopy. CSA was administered alone, with the nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) or with exogenous NOS substrate L-arginine. CSA significantly constricted the whole of the renal microvasculature whereas L-NAME alone preferentially constricted the preglomerular vessels. L-Arginine reversed the vasoconstriction induced by CSA whereas L-NAME had no further effect. Preglomerular basal vascular tone is dependent on continuous production of NO and alterations in the L-arginine-NO pathway contribute to CSA-induced renal vasoconstriction.

Animals↗
PubMed1994

Major hepatic resection under total vascular exclusion with extracorporeal venovenous bypass.

Techniques and principles pioneered during the development of hepatic transplantation have now been applied to hepatic resectional surgery. Primary and metastatic hepatic neoplasms that are centrally located or in proximity to the vena cava or major branches have been resected successfully by total hepatic vascular exclusion. Herein, the authors report the use of extracorporeal venovenous bypass from the infrahepatic vena cava to the axillary vein to provide adequate central venous filling during total vascular exclusion. The use of this technology, pioneered in transplantation, has extended the indication for hepatic resection to patients previously considered unresectable.

Axillary Vein↗
PubMed1993

In vivo effects of endothelin on the renal microcirculation.

Endothelin-1 (ET) is a recently discovered vasoconstrictor peptide which is released by renal vascular endothelial cells in response to a number of pathologic insults including ischemia, endotoxemia, bacteremia, and cyclosporine nephrotoxicity. Because microvascular vasoconstriction is an integral component of the acute renal dysfunction associated with these conditions, this study was undertaken to determine the in vivo effects of ET on the renal microcirculation. We used the split hydronephrotic kidney model in decerebrate Sprague-Dawley rats to study vessel diameter and red cell velocity responses to ET using intravital videomicroscopy and doppler velocimetry. Topical administration of increasing concentrations of ET caused a dose-dependent constriction of interlobular arteries which reached a maximum of 27 +/- 5% at an ET concentration of 10(-8) M. A corresponding decrease of 64 +/- 8% in interlobular arterial blood flow was observed. Afferent and efferent arteriole diameters were reduced by 39 +/- 2% and 27 +/- 5%, respectively. These vascular effects were completely prevented by the systemic preinfusion of anti-endothelin antiserum. Infusion of antiserum alone had no effect on systemic hemodynamics or renal microvascular variables, suggesting that ET has little or no role in maintaining basal vascular tone in the kidney. We conclude that ET is a potent in vivo constrictor of the renal microcirculation and may be involved in mediating pathologic vasoconstriction.

Animals↗
PubMed1993

Escherichia coli bacteremia exacerbates cyclosporine-induced renal vasoconstriction.

The clinical observation that cyclosporine (CSA) nephrotoxicity is particularly severe in patients during and following bacterial infections has recently been made. Transplant recipients develop a marked deterioration of graft function following Escherichia coli bacteremia secondary to urinary tract infection. CSA causes intrarenal vasoconstriction which may account for its nephrotoxicity. We therefore undertook a study using the split hydronephrotic kidney model to investigate the direct in vivo effects of CSA and E. coli bacteremia on the renal microcirculation. Hydronephrotic kidneys in Sprague-Dawley rats were suspended in an environmentally controlled tissue bath. Interlobular arterial (ILA) and afferent (AFF) and efferent (EFF) arteriolar diameters were measured by in vivo videomicroscopy and red cell velocity by Doppler velocimetry. Topical administration of CSA to the kidney in the tissue bath caused a 23 +/- 1% constriction of the ILA and a 67 +/- 5% reduction in blood flow. AFF and EFF arterioles were also constricted by 21 +/- 3 and 16 +/- 2%, respectively. The intravenous infusion of live E. coli was also followed by decreases in ILA diameters and flow (38 +/- 4 and 68 +/- 4%) and AFF diameters (22 +/- 5%) while EFF diameters were unchanged. The infusion of E. coli following addition of CSA to the tissue bath resulted in a dramatically increased constriction of ILA (49 +/- 4%) and AFF (31 +/- 2%) vessels and almost abolished ILA flow (90 +/- 2%). We conclude that in this model, E. coli bacteremia exacerbates CSA-induced preglomerular vasoconstriction and suggests a scientific basis for the severe renal dysfunction noted in transplant recipients during bacterial infection.

Animals↗
PubMed1993

Acute cyclosporine-induced renal vasoconstriction is mediated by endothelin-1.

BACKGROUND: Cyclosporine causes intrarenal vasoconstriction, which may account for its nephrotoxic side effects. Plasma levels of the vasoconstrictor peptide endothelin-1 are increased after cyclosporine administration, and endothelin-1 has been shown to cause renal vasoconstriction. In this study we used in vivo microscopy to investigate the role of endothelin-1 in cyclosporine-induced vasoconstriction. METHODS: Hydronephrotic kidneys in decerebrate rats were suspended in an environmentally controlled tissue bath with neurovascular supply intact. Interlobular, afferent, and efferent arteriolar diameters and flow were measured by videomicroscopy and Doppler velocimetry. Cyclosporine was added to the tissue bath, and measurements were repeated for 60 minutes. In study groups endogenous endothelin-1 was blocked by infusion of either specific endothelin antiserum or an endothelin-1 receptor antagonist. RESULTS: Cyclosporine caused constriction of the interlobular artery by 20% +/- 2% and a corresponding decrease in blood flow by 66% +/- 4%. The afferent and efferent arterioles constricted to a similar degree. This vasoconstriction was entirely prevented by infusion of either the endothelin antiserum or the receptor antagonist. The antagonist reagents alone had no effect on hemodynamic parameters or renal microvessel diameters. CONCLUSIONS: The acute renal vasoconstriction induced by cyclosporine is mediated by endothelin-1. Endogenous endothelin-1 has little role in maintaining basal vascular tone.

Animals↗
PubMed1992

In vivo assessment by videomicroscopy of acute renal microvascular responses to cyclosporin.

Nephrotoxicity limits the use of cyclosporin A for immunosuppression after organ transplantation and may be caused by glomerular hypoperfusion. Indirect studies have shown that cyclosporin A increases renal vascular resistance and reduces total renal blood flow. This study used direct in vivo videomicroscopy to define the effects of the drug on the renal microcirculation of the rat. An intravenous infusion of cyclosporin A (20 mg per kg body-weight) caused a 13 per cent acute constriction of the proximal interlobular artery and an associated 29 per cent reduction in preglomerular interlobular arterial blood flow. There was a simultaneous increase in mean arterial blood pressure of 34 per cent caused by cyclosporin A and a 23 per cent increase in systemic vascular resistance. Cyclosporin acutely reduces renal microvascular blood flow by vasoconstriction and affects the central circulation, suggesting that a generalized peripheral vasoconstriction is induced.

Animals↗
PubMed1992

Superior results with combined kidney-pancreas transplants.

From February of 1987 to February of 1991 the authors performed 23 pancreas transplants for Type I diabetes mellitus. Eight of the pancreas transplants were in patients who had a previous kidney transplant, 14 were simultaneous kidney and pancreas transplants, and 1 was in a pre-uremic diabetic. Two patients have been retransplanted after losing first grafts. All pancreata were retrieved from heart-beating cadaver donors. Pancreata were transplanted into the iliac fossa of the recipient using the iliac artery and vein as arterial inflow and venous outflow, respectively. Drainage of the pancreatic ductal system was accomplished by anastomosing either a patch or segment of duodenum surrounding the ampulla of Vater to the urinary bladder. All pancreata functioned initially with no patient requiring insulin 6 hours after surgery. Two grafts were lost early due to thrombosis of the venous drainage of the transplant; 4 grafts were lost to acute rejection; 3 were lost to chronic rejection; and 1 patient died with a functioning pancreas. One-year graft survival for all pancreatic grafts is 62 per cent. One-year patient survival is 96 per cent. One-year pancreatic graft and patient survival for the 14 combined kidney-pancreas transplants is 88 per cent and 100 per cent, respectively. Two kidneys transplanted with pancreata also were lost to acute rejection. Pancreas transplantation has proven to be a viable treatment alternative for selected patients with Type I diabetes mellitus. Long-term results are best when pancreas transplantation is done in combination with renal transplantation.

Adult↗
PubMed1992

Kentucky's first liver transplant program.

Forty-nine patients have been referred to our institution for evaluation of orthotopic liver transplantation since our program started in 1990. Fourteen patients have been excluded for medical or psychosocial reasons. Eleven were accepted for future transplantations and are reevaluated every 3 months. Eight patients died while waiting for a suitable donor. Sixteen patients have undergone transplantations. One patient underwent transplantation a second time for refractory rejection of the first allograft. Five patients have died after liver transplantation. Eleven recipients are alive and well. Nine of the 11 have returned to normal activity.

Humans↗
PubMed1991

The influence of the cyclosporine vehicle, cremophor EL, on renal microvascular blood flow in the rat.

Cyclosporine nephrotoxicity may be due to glomerular hypoperfusion. Previous experimental and clinical studies have demonstrated a decrease in renal blood flow and an increase in renal vascular resistance. Cremophor EL, which is the vehicle in which CsA is dissolved, is thought to be a factor involved in intrarenal arteriolar vasoconstriction. To determine the relative contributions of the vehicle and CsA to intrarenal arteriolar vasoconstriction, we used in vivo videomicroscopy and Doppler velocimetry to measure changes in renal microvascular blood flow in the rat. A 5-min intravenous infusion of 20 mg/kg of CsA resulted in a 17% mean reduction (P less than 0.05) in the diameter of preglomerular interlobular arterioles and an associated 60% reduction (P less than 0.05) in microvascular blood flow by 15 min. Cremophor EL/ethanol equivalent caused less vasoconstriction (up to 10%) but resulted in a 42% mean decrease (P less than 0.05) in microvascular blood flow, probably secondary to a 38% mean decrease (P less than 0.05) in cardiac output and 13% decrease in arterial pressure. We conclude that cremophor EL does contribute to in vivo reduction of preglomerular microvascular blood flow in the rat. This may be particularly important when using this intravenous preparation in the study of CsA nephrotoxicity.

Animals↗
PubMed1991

The role of intrarenal prostaglandins and angiotensin II in acute cyclosporine-induced vasoconstriction.

Cyclosporine causes intrarenal vasoconstriction, which may account for its nephrotoxic effects. In this study we investigated the role of endogenous prostaglandins and angiotensin II in cyclosporine-induced intrarenal vasoconstriction. Split hydronephrotic kidneys in decerebrate rats (n = 16) were suspended in an environmentally controlled tissue bath. Interlobular, afferent, and efferent arteriolar diameters and red blood cell velocity were measured by in vivo video-microscopy and Doppler velocimetry. After topical application of cyclosporine to the kidney in the tissue bath, a 12% +/- 2% constriction of the interlobular and a 28% +/- 5% reduction in interlobular blood flow occurred. The afferent and efferent arterioles also constricted by 13% +/- 2% and 10% +/- 3%, respectively. Prostaglandin inhibition with mefenemate augmented this vasoconstriction (16% +/- 2% at interlobular and 21% +/- 4% at afferent arterioles) and reduction in interlobular blood flow (38% +/- 8%) below baseline values. Mefenemate alone resulted in a 35% +/- 5% reduction in interlobular blood flow, which was not further augmented by cyclosporine. In contrast, local competitive angiotensin II-receptor inhibition with saralasin maintained blood flow after cyclosporine and prevented intrarenal vasoconstriction by cyclosporine. This suggests that prostaglandins protect against intrarenal vasoconstriction and that acute cyclosporine-induced vasoconstriction is mediated through angiotensin II receptors.

1-Sarcosine-8-Isoleucine Angiotensin II↗