Biomedical subjects

E Hodge

Publications and source records attributed to E Hodge.

At least 19 recordsLinked to original sources

PubMed2001

Ruminant brain ribonucleases: expression and evolution.

Molecular evolutionary analyses of mammalian ribonucleases have shown that gene duplication events giving rise to three paralogous genes occurred in ruminant ancestors. One of these genes encodes a ribonuclease identified in bovine brain. A peculiar feature of this enzyme and orthologous sequences in other ruminants are C-terminal extensions consisting of 17-27 amino acid residues. Evidence was obtained by Western blot analysis for the presence of brain-type ribonucleases in brain tissue not only of ox, but also of sheep, roe deer and chevrotain (Tragulus javanicus), a member of the earliest diverged taxon of the ruminants. The C-terminal extension of brain-type ribonuclease from giraffe deviates much in sequence from orthologues in other ruminants, due to a change of reading frame. However, the gene encodes a functional enzyme, which could be expressed in heterologous systems. The messenger RNA of bovine brain ribonuclease is not only expressed at a high level in brain tissue but also in lactating mammary gland. The enzyme was isolated and identified from this latter tissue, but was not present in bovine milk, although pancreatic ribonucleases A and B could be isolated from both sources. This suggests different ways of secretion of the two enzyme types, possibly related to structural differences. The sequence of the brain-type RNase from chevrotain suggests that the C-terminal extensions of ruminant brain-type ribonucleases originate from deletions in the ancestral DNA (including a region with stop codons), followed by insertion of a 5-8-fold repeated hexanucleotide sequence, coding for a proline-rich polypeptide.

Amino Acid Sequence↗

PubMed1999

Prednisone withdrawal in kidney transplant recipients on cyclosporine and mycophenolate mofetil--a prospective randomized study. Steroid Withdrawal Study Group.

BACKGROUND: Prospective randomized trials have shown a reduced rate of acute rejection (AR) in mycophenolate mofetil-treated kidney transplant recipients. We hypothesized that this increased protection from AR could allow successful prednisone (P) withdrawal in cyclosporine/mycophenolate mofetil/P-treated recipients. METHODS: A multicenter, prospective, randomized, double-blind trial of P withdrawal at 3 months post-transplant was initiated. Entry criteria were: primary transplant, adult, no AR by 90 days, mycophenolate mofetil dose > or =2 g/day, cyclosporine dose = 5-15 mg/kg/ day, P dose = 10-15 mg/day. Study participants were randomized to have P tapered over 8 weeks (beginning at 3 months posttransplant) to 0 vs. 10 mg/day. Prestudy power analysis determined 500 recipients should be randomized for 80% statistical power to test equivalence of the primary endpoint, AR, or treatment failure at 1 year posttransplant. By design, the study was to be stopped if interim data precluded reaching equivalence. An established data safety monitoring board monitored the study. RESULTS: After 266 patients were enrolled, the patient enrollment was stopped (after safety monitoring board review) because of excess rejection in the P withdrawal group. The Kaplan-Meier estimate of the cumulative incidence of rejection or treatment failure within 1 year posttransplant (+/-95% confidence interval) for the maintenance group was 9.8% (4.4%; treatment failure, 14.9%); for the withdrawal group, 30.8% (21.0%; 39.3%). Treatment differences in the distribution of time to event were highly significant (P = 0.0007). Of note, risk was higher in blacks (39.6%) versus nonblacks (16.0%) (P<0.001). At 1 year post-transplant, there was no difference between groups in patient or graft survival. For the patients with functioning grafts at 6 months posttransplant, withdrawal patients had lower cholesterol (P = 0.0005), had higher creatinine (P = 0.03), and were less likely to use antihypertensives (P = 0.001). These differences persist to 1 yr posttransplant. CONCLUSIONS: We conclude that for recipients on cyclosporine/mycophenolate mofetil/P with no AR at 90 days, the chance of developing subsequent AR is small; if P is tapered and withdrawn, the risk increases (but the majority remain free of acute and chronic rejection). After withdrawal, the risk of AR is different for blacks versus nonblacks. Withdrawal patients had a lower cholesterol level and less need for antihypertensives.

Adolescent↗

PubMed1999

Adenoviral-mediated gene transfer induces sustained pericardial VEGF expression in dogs: effect on myocardial angiogenesis.

OBJECTIVE: Angiogenic peptides like VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor) have entered clinical trials for coronary artery disease. Attempts are being made to devise clinically relevant means of delivery and to effect site-specific delivery of these peptides to the cardiac tissue, in order to limit systemic side-effects. We characterized the response of the pericardium to delivery of a replication-deficient adenovirus carrying the cDNA for AdCMV.VEGF165, and assessed the effect of pericardial VEGF165 on myocardial collateral development in a canine model of progressive coronary occlusion. METHODS: Ameroid constrictors were placed on the proximal left circumflex coronary artery of mongrel dogs. Ten days later, 6 x 10(9) pfu AdCMV.VEGF165 (n = 9). AdRSV.beta-gal (n = 9), or saline (n = 7) were injected through an indwelling pericardial catheter. Transfection efficiency was assessed by X-gal staining. Pericardial and serum VEGF levels were measured serially by ELISA. Maximal myocardial collateral perfusion was quantified with radiolabeled or fluorescent microspheres 28 days after treatment. RESULTS: In AdRSV.beta-gal-treated dogs, there was extensive beta-gal staining in the pericardium and epicardium, with minimal beta-gal staining in the mid-myocardium and endocardium. Pericardial delivery of AdCMV.VEGF165 resulted in sustained (8-14 day) pericardial transgene expression, with VEGF levels peaking 3 days after infection (> 200 ng/ml) and decreasing thereafter. There was no detectable increase in serum VEGF levels. Maximal collateral perfusion, a principal correlate of collateral development and angiogenesis, was equivalent in all groups. CONCLUSION: Adenoviral-mediated gene transfer is capable of inducing sustained VEGF165 expression in the pericardium; however, locally targeted pericardial VEGF delivery failed to improve myocardial collateral perfusion in this model.

Adenoviridae↗

PubMed1997

Pharmacodynamics of basic fibroblast growth factor: route of administration determines myocardial and systemic distribution.

OBJECTIVE: We have shown that basic fibroblast growth factor (bFGF/FGF-2) enhances myocardial collateral development in a canine model of progressive coronary occlusion when delivered via the left atrial or intracoronary routes; however, we have found intravenous bFGF ineffective in the same model. Data on the fate and efficacy of intravenous bFGF are limited. We hypothesized that first pass lung uptake might limit myocardial bFGF availability after intravenous injection. We postulated that delivery of bFGF through the distal port of a wedged Swan Ganz catheter might circumvent this problem by restricting exposure of bFGF to a limited number of pulmonary binding sites. This study evaluated differential regional uptake of 125I labeled bFGF following bolus intravenous, Swan Ganz, left atrial, intracoronary, and pericardial delivery. METHODS: Mongrel dogs were used. Human recombinant bFGF, monoiodinated with 125I, was mixed with cold bFGF to a specific activity of 0.03 microCi/microgram. Approximately 100 micrograms/kg was injected per animal by the intravenous, left atrial, Swan Ganz, intracoronary, or pericardial route. Dogs were killed 15 min or 150 min later. The heart, lungs, liver, spleen, and kidneys were harvested and 125I activity was assessed. Immunohistochemical and pharmacokinetic studies were also performed. RESULTS: Serum half life of bFGF was comparable after intracoronary, intravenous and left atrial delivery (50 min); however, there were significant differences with regard to pharmacodynamics. After intracoronary administration, 3-5% of the total bFGF dose was recovered from the heart, with the peptide immunolocalized to the extracellular matrix and vascular endothelium. In contrast, only 1.3% of the injected bFGF was localized to the heart after left atrial administration and 0.5% was recovered after intravenous or Swan Ganz delivery. Pericardial administration resulted in substantial cardiac bFGF delivery; 19% was present at 150 min. Myocardial uptake was similar with Swan Ganz and intravenous delivery, suggesting that the administered dose did not saturate available pulmonary binding sites. CONCLUSIONS: These data predict efficacy of intracoronary, left atrial, and pericardial bFGF for myocardial angiogenesis, and a lack of efficacy after bolus intravenous and Swan Ganz administration.

Animals↗

PubMed1997

Comparable dose-dependent inhibition of AP-7 sensitive strychnine-induced allodynia and paw pinch-induced nociception by mexiletine in the rat.

The blockade of spinal glycine receptors with intrathecal (i.t.) strychnine produces segmentally-localized allodynia in the rat; a reversible and highly reproducible effect that is attained without peripheral or central nerve injury. We investigated the effect of i.v. mexiletine, an orally active congener of lidocaine, on strychnine allodynia and compared the dose-response relationship of mexiletine in normal (noxious paw pinch) versus abnormal (i.t. strychnine) nociceptive conditions. In addition, we determined the dose-response effect of i.t. AP-7 (an NMDA antagonist) on strychnine allodynia. Male, Sprague-Dawley rats, fitted with chronic i.t. catheters, were lightly anesthetized with urethane. Stimulus evoked changes in blood pressure and heart rate were recorded from the left carotid artery and cortical electroence-phalographic (EEG) activity was continuously monitored using subdermal needle electrodes. After i.t. strychnine (40 micrograms), repetitive brushing of the hair (hair deflection) evoked a progressive increase in mean arterial pressure and heart rate, an abrupt motor withdrawal response, and desynchronization of the EEG, equivalent to those elicited by the chemical nociceptive agent, mustard oil (without strychnine). Pretreatment with mexiletine (5-30 mg/kg i.v. 5 min before i.t. strychnine) dose-dependently inhibited the responses evoked by noxious hind paw pinch (no strychnine) and hair deflection (after i.t. strychnine) with equal potency (ED50's = 9.1-17 mg/kg). Below 30 mg/kg, this effect was achieved without a change in EEG synchrony (cortical activity reflecting the level of anesthesia) and without affecting motor efferent pathways. Strychnine allodynia was also significantly blocked by i.t. AP-7. The ED50's and 95% confidence intervals were 1.1 micrograms (0.7-1.8) for mean arterial pressure, 1.7 micrograms (0.5-6.0) for heart rate, and 0.4 microgram (0.07-2.0) for withdrawal duration. Cortical EEG synchrony was unchanged after i.t. AP-7 consistent with a spinal site of action. The data indicate that: (i) robust allodynia can be selectively induced with i.t. strychnine in animals whose somatosensory systems are otherwise normal; (ii) sub-anesthetic doses of i.v. mexiletine inhibit the abnormal responses to low-threshold (A-fiber) afferent input in the strychnine model of allodynia (i.e., in the absence of peripheral or central nerve injury) at doses which affect normal nociception; and (iii) in the presence of i.t. strychnine, low-threshold afferent input activates a spinal NMDA-receptor mediated process normally restricted to noxious afferent input. Systemic mexiletine may have an important spinal site of action in abnormal pain states.

2-Amino-5-phosphonovalerate↗

PubMed1997

Effect of basic fibroblast growth factor on myocardial angiogenesis in dogs with mature collateral vessels.

OBJECTIVES: We sought to evaluate the potential of basic fibroblast growth factor (bFGF) to enhance coronary collateral perfusion in dogs with chronic single-vessel coronary occlusion. A secondary goal was to examine whether the salutary effects of bFGF treatment, previously proved effective in the short term, would be maintained in the long term (6 months). BACKGROUND: bFGF, an angiogenic growth factor, is currently the subject of a Phase I trial in patients with ischemic heart disease. It has been shown to promote collateral development in dogs with progressive coronary occlusion when given during the period of natural collateralization. The effect of bFGF on quiescent collateral vessels, a subject of significant clinical importance, is uncertain. METHODS: Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF (1.74 mg/day for 7 days), a regimen previously proved effective, or to saline solution. Maximal collateral perfusion was assessed 6 months later, and the dogs were reassigned to a course of bFGF or saline solution. Collateral perfusion was reevaluated after the second treatment course. RESULTS: At 6 months, collateral function was identical in the groups treated initially with bFGF and saline solution. The subsequent course of bFGF did not induce further collateralization. CONCLUSIONS: Although we previously demonstrated the salutary effects of this bFGF regimen in the short term (5 weeks), collateral flow in control dogs reached parity with that of bFGF-treated dogs after 6 months. bFGF did not induce further collateralization in dogs with mature collateral vessels, underscoring the priming role of ischemia for bFGF-induced collateral development.

Animals↗

PubMed1996

Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury.

BACKGROUND: We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) enhance canine coronary collateral development when administered for > or = 4 weeks. bFGF, a pluripotent mitogen of mesodermally derived cells, could theoretically exacerbate neointimal smooth muscle cell hyperplasia, a fundamental component of atherosclerosis. VEGF, an endothelial cell-specific mitogen and vascular permeability factor, could have deleterious effects related to vascular hyperpermeability. The present investigation had two aims: (1) to ascertain whether brief (7-day) systemic arterial treatment with bFGF or VEGF would improve myocardial collateral perfusion and (2) to determine whether these peptides induce neointimal accumulation in vivo. METHODS AND RESULTS: Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF 1.74 mg (n = 9), VEGF 0.72 mg (n = 9), or saline (n = 10) as a daily left atrial bolus (days 10 to 16). Additional dogs were randomized to VEGF 0.72 mg (n = 6) or saline (n = 5); however, treatment was delayed by 1 week. Coincident with the institution of treatment, all dogs underwent balloon denudation injury of the iliofemoral artery. bFGF markedly increased maximal collateral flow but did not exacerbate neointimal accumulation. VEGF had no discernible effect on maximal collateral flow, but it exacerbated neointimal thickening after vascular injury. CONCLUSIONS: Short-term treatment with bFGF enhanced collateral development without increasing neointimal accumulation at sites of vascular injury. Although VEGF did not increase collateral development as administered in this study, it significantly exacerbated neointimal accumulation. These data provide support for the clinical investigation of bFGF in selected patients with ischemic heart disease.

Animals↗

PubMed1996

Cadaveric kidney transplantation under prophylactic polyclonal antibody immunosuppression with anti-lymphoblast globulin versus anti-thymocyte globulin.

OBJECTIVES: This retrospective study was undertaken to evaluate and compare the clinical and immunologic outcomes following prophylactic induction treatment with Minnesota anti-lymphoblast globulin (MALG) and Upjohn anti-thymocyte globulin (ATGAM) in cadaver renal transplantation. METHODS: From 1990 to 1994, 63 patients with renal transplants from cadavers received MALG and 77 patients received ATGAM for induction treatment. Most pretransplant parameters were equivalent in both groups. There was no significant difference in the total dose and mean duration of MALG/ATGAM administration. The post-transplant outcome in these groups was compared. RESULTS: There was no difference between the MALG and ATGAM groups with respect to the overall number of rejection episodes, median days to rejection, or the number of steroid-resistant rejection episodes. However, MALG-treated patients experienced a greater number of rejections in the first 60 days postoperatively (P = 0.06). There was no difference in the nadir serum creatinine level in the first 20 postoperative days in the two groups; however, it took fewer days to reach the nadir in the ATGAM group (P = 0.03). The incidence of delayed graft function was higher in the MALG group than in the ATGAM group (38% versus 31%) but not statistically significant. Graft survival at 12 and 24 months was comparable in both groups. However, patient survival was superior at 12 and 24 months in ATGAM-treated transplant recipients (P = 0.03). The mean serum creatinine at 6, 12, and 24 months was similar in both the MALG and ATGAM groups. The mean fall and recovery of CD3, CD4, and CD8 T-lymphocyte subsets while on MALG/ATGAM were similar in both groups. The incidence of infectious complications was greater in the MALG group. CONCLUSIONS: MALG and ATGAM have comparable clinical immunosuppressive effects. Patients receiving ATGAM experienced fewer rejections in the first 2 months, fewer infections, and better survival.

Antilymphocyte Serum↗

PubMed1996

5-HT2 receptor involvement in conditioned olfactory learning in the neonate rat pup.

These experiments addressed the role of 5-HT2 receptors in conditioned olfactory learning. Ritanserin, a 5-HT2A/2C antagonist, was injected subcutaneously into postnatal day (PND) 7 pups before or after conditioned olfactory training to a peppermint odor. When the pups were tested for olfactory preference on PND 8, those injected with ritanserin before training failed to acquire an odor preference whereas those injected after training learned. This suggested that the 5-HT2 receptor is required only in the acquisition of conditioned olfactory learning. Injection of ritanserin directly into the olfactory bulb before training also blocked preference for the peppermint odor. In pups that had depletion of the 5-HT input to the bulb, subcutaneous injection of a 5-HT2A/2C agonist was sufficient to maintain conditioned olfactory learning, confirming the importance of 5-HT in learning.

Animals↗

PubMed1996

Successful renal transplantation in a patient with large granular lymphocytic leukemia with natural killer cell proliferation.

A patient with advancing renal failure attributed to focal segmental glomerulosclerosis was found to have marked NK (CD56+) cell expansion and large granular lymphocytic leukemia. Subsequent living-related renal transplantation was accomplished with two early bouts of acute cellular rejection requiring therapy with methylprednisolone and monoclonal antibody OKT3. Chronic triple drug immunosuppressive therapy has substantially reduced the marked NK (CD56+) proliferation. The renal transplantation remains successful after 15 months despite persistent but reduced numbers of circulating NK cells, the potential role of which in the pathogenesis of the underlying nephropathy or the cellular rejection process remains speculative.

Adult↗

PubMed1996

Long-term results with single pediatric donor kidney transplants in adult recipients.

PURPOSE: We investigated whether transplantation of single pediatric donor kidneys into adults leads to an increased incidence of functional allograft impairment and complications, as previously reported. MATERIALS AND METHODS: To evaluate long-term functional outcome using single pediatric donor kidneys 60 adults (study group) who underwent transplantation between March 1973 and December 1988 using single pediatric donor kidneys 6 years old or younger (mean donor age plus or minus standard deviation 41.1 +/- 17.9 months) were compared to 58 matched adults (control group) who underwent transplantation with adult kidneys (mean donor age 29.7 +/- 10.8 years). The groups were identical for era of transplantation, recipient age, sex and followup (82 versus 83 months). RESULTS: There was no difference in patient survival between the study and control groups (p = 0.26). In the study group there were an increased requirement for early dialysis (45 versus 24%, p = 0.02), a higher incidence of proteinuria (greater than 0.8 gm./24 hours, 67 versus 48%, p = 0.04) and a higher incidence of rejection within the first 6 months (80 versus 64%, p = 0.05). There was also an increased incidence of graft failure from acute rejection in the study group. Early differences in serum creatinine levels in the 2 groups dissipated after 3 months. Renal allograft histopathology revealed no significant difference in the incidence of focal segmental glomerulosclerosis in the study versus control groups after transplantation (22.9 versus 13.3%, p = 0.70). However, focal segmental glomerulosclerosis manifested sooner after transplantation in study than control patients (mean 37 versus 82 months). After transplantation proteinuria developed in study patients with focal segmental glomerulosclerosis at a mean of 4.6 months compared to 31.8 months in controls with post-transplant focal segmental glomerulosclerosis. Graft survival in the study group was superior when cyclosporine was given rather than conventional noncyclosporine based immunosuppression. Five-year graft survival rates were 48 versus 44% for cyclosporine treated and 33 versus 44% for conventionally treated study versus control patients. CONCLUSIONS: These data suggest that with cyclosporine immunosuppression transplanting single pediatric kidneys into adults yields the same long-term functional graft outcome as adult donor kidneys.

Adult↗

PubMed1995

Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart.

BACKGROUND: Recently we reported that intracoronary administration of basic fibroblast growth factor (bFGF), a potent angiogenic peptide, increases collateral blood flow in dogs subjected to progressive left circumflex coronary artery (LCx) occlusion. The aim of the present study was to examine the effect of systemically administered bFGF on collateral blood flow and to assess its pharmacokinetics and potential side effects. METHODS AND RESULTS: Forty-seven dogs were subjected to progressive ameroid-induced occlusion of the LCx, an intervention known to induce the development of collateral vessels. In phase I of the investigation, dogs were randomized to receive bFGF 1.74 mg/d (n = 10) or saline (n = 9) as a left atrial injection for 4 weeks. Relative collateral blood flow was assessed serially with radiolabeled microspheres in the conscious state during maximal coronary vasodilatation. Initiation of bFGF treatment was temporally associated with a marked acceleration of collateral development; however, collateral flow in control dogs improved toward the end of the study, approaching that of bFGF-treated dogs at the 38-day end point. Phase II of the investigation was a three-armed study of extended duration to determine whether bFGF caused a sustained increase in collateral function. Dogs were randomized to receive bFGF 1.74 mg/d for 9 weeks (n = 7), bFGF 1.74 mg/d for 5 weeks followed by placebo for 4 weeks (n = 11), or placebo for 9 weeks (n = 10). Relative and absolute collateral blood flow were assessed serially with microspheres during maximal coronary vasodilatation. Between the 10th and 17th days after ameroid placement, bFGF-treated dogs exhibited marked improvement in collateral flow such that maximal collateral conductance exceeded that of controls by 24% at the 5-week crossover point. Final collateral conductance was similar in dogs receiving bFGF for 5 and 9 weeks despite withdrawal of treatment in the former group. bFGF administration was associated with a 21% increase in final collateral conductance as well as a 49% increase in collateral zone vascular density. Prolonged bFGF administration was also associated with a decrease in arterial pressure, moderate thrombocytopenia, and moderate, reversible anemia. CONCLUSIONS: Systemic administration of bFGF enhanced collateral conductance in dogs with progressive single-vessel coronary occlusion. The beneficial effect of bFGF occurred primarily between the 7th and 14th days of therapy, and regression of collateral development was not noted after withdrawal of treatment. The present investigation provides impetus to the concept that collateral development can be enhanced pharmacologically-specifically by bFGF-raising the possibility that such an intervention might eventually be applied clinically.

Animals↗

PubMed1995

Long-term renal function in cyclosporine-treated renal allograft recipients.

OBJECTIVES: The purpose of this study was to analyze the factors affecting long-term renal function in cyclosporine-treated kidney transplants. METHODS: The study population comprised 167 patients with more than 5 years of graft function on cyclosporine therapy. Patients were subdivided into those with a serum creatinine level 2.0 mg/dL or less (group I, n = 123) versus those with a level more than 2.0 mg/dL (group II, n = 44) at 5 years post-transplant. Patient survival, graft survival, rejection episodes, renal function, cyclosporine dose and trough level, and proteinuria were compared in these two groups. RESULTS: There was no significant difference between groups I and II in terms of race, sex, donor source, donor age, primary renal disease, retransplants, transfusions, presensitization, histocompatibility locus antigen match, or initial nonfunction. At 6 months post-transplantation, the mean serum creatinine level in group II was significantly higher than group I (P = 0.00001), and this difference increased at subsequent follow-up intervals. The incidence of proteinuria was significantly higher in group II compared with group I (P < 0.001). Renal allograft survival beyond 5 years post-transplant was significantly better in group I compared with group II (P = 0.005). There was no significant difference in the mean cyclosporine dose or the mean cyclosporine trough level between groups I and II at any time following transplantation. The most important difference between groups I and II was the finding of significantly more early (P < 0.001) and late (P < 0.001) rejection episodes in group II. CONCLUSIONS: These data suggest that long-term renal function in cyclosporine-treated kidney transplant patients is primarily influenced by the occurrence of early and late rejection episodes rather than by the dosage or duration of cyclosporine therapy.

Adult↗

PubMed1994

The value of prostatic specific antigen in prostate cancer screening in the community.

At a one-day screening for prostate cancer in 1991, a urologist evaluated 142 men ages 50 years-84 years (mean: 67 years) utilizing a digital rectal exam (DRE), serum prostatic specific antigen (PSA), and a detailed questionnaire. The 44 men with an abnormal DRE and/or PSA were recontacted by letter one year later to determine the outcome. By 12 months, 31 men (70%) with abnormal findings had seen a physician as recommended. Of the 13 men followed with abnormal DRE only, three were biopsied with no cancer found. Of the 11 with an elevated PSA only, six were biopsied and two had cancer. Of the men with both abnormal PSA and DRE, six were biopsied and two had cancer. Thus, after 12 months, the preliminary cancer detection rate was 2.8% for the entire study population, 22% for those with an elevated PSA, and 10% for those with an abnormal DRE. The results suggest that the use of PSA combined with DRE is a more efficient strategy for detecting prostate cancer than DRE alone.

Adenocarcinoma↗

PubMed1993

Percutaneous management of transplant ureteral fistulas: patient selection and long-term results.

Of 24 renal allograft recipients with urinary extravasation 14 (58%) with ureteral fistulas were selected for percutaneous management in an attempt to obviate secondary operative intervention. The initial procedure in all cases was placement of a percutaneous nephrostomy tube with subsequent internal or internal/external stenting. With a mean followup of 47 months, the percutaneous management proved definitive in 5 patients (36%) and palliative in 1 (7%). The other 8 patients (57%) subsequently required open operative intervention. With this study, we conclude that percutaneous techniques can provide long-term definitive management for at least some transplant ureteral fistulas. However, even in a highly selected group of patients success rates will be limited.

Follow-Up Studies↗

PubMed1993

Preoperative hospitalization to hydrate living kidney donors can be omitted without sacrificing graft function.

This prospective study was done to determine whether preoperative hospitalization for hydration of living kidney donors could be omitted without sacrificing graft function in the recipient. The study group consisted of 36 consecutive kidney donors who underwent donation on a "to come in" basis. Fluid management consisted of 1 l. lactated ringer's solution per hour beginning 2 hours preoperatively. The control group was hospitalized preoperatively for intravenous hydration of an equivalent amount of saline solution given for 12 to 16 hours. No recipient of the study group donors experienced delayed graft function. Furthermore, in that group immediate and longer term graft function, as defined by immediate graft output, serum creatinine on postoperative day 1 and nadir serum creatinine levels, was equivalent to or better than that in the control group. We conclude that a rapid infusion of saline solution in the immediate preoperative period can replace overnight intravenous hydration of living kidney donors, and that the result will be a significant reduction in overall hospital stay for the donor without compromise in graft function for the recipient.

Adult↗

PubMed1993

A model to assess interventions to improve collateral blood flow: continuous administration of agents into the left coronary artery in dogs.

OBJECTIVE: The aim was to develop an experimental model in which angiogenic growth factor(s) could be targeted locally to enhance myocardial collateral formation. A preparation was developed in which agents could be infused selectively into the left main coronary artery on a chronic basis to assess the potential of acidic fibroblast growth factor (FGF) to improve collateral blood flow. METHODS: Ameroid constrictors were placed on the left circumflex coronary artery of mixed hounds. Five weeks after ameroid placement, the artery was ligated and transected at the point of ameroid occlusion; a catheter was inserted and passed retrogradely into the left main coronary artery. The catheter was connected to an implantable infusion pump that provided continuous intracoronary drug infusion for 4 weeks. Dogs were randomised to receive acidic FGF with heparin (30 micrograms.h-1 and 30 IU.h-1, respectively, n = 16) or heparin alone (30 IU.h-1, n = 14). Regional myocardial blood flow was determined in the conscious state at the beginning and end of treatment. RESULTS: There were no deaths or important surgical complications related to the establishment of the coronary artery infusions. During the treatment interval (5-9 weeks after ameroid placement) the ratio of maximum ischaemic zone/normal zone blood flow increased from 0.39(SD 0.10) to 0.50(0.11) (p < 0.01) in dogs treated with acidic FGF plus heparin; however, similar improvement was noted in dogs treated with heparin alone. Ischaemic zone and normal zone vascular density was also equivalent in the two groups. CONCLUSIONS: This preparation makes possible the chronic intracoronary administration of agents which may promote myocardial angiogenesis, and allows assessment of collateral blood flow before and after treatment. As given in this investigation, acidic FGF had no demonstrable effect on collateral blood flow; however, this model may facilitate the identification of agents that do enhance myocardial collateral formation.

Animals↗

PubMed1993

Extracardiac to coronary anastomoses support regional left ventricular function in dogs.

Intramyocardial implantation of a systemic artery [the internal mammary artery (IMA)] causes angiogenesis, with formation of systemic to coronary anastomoses. In dogs, we assessed the magnitude of IMA-derived nutritive flow and determined its influence on regional contraction. We also sought to determine whether acidic fibroblast growth factor (FGF), an angiogenic peptide, could enhance myocardial neovascularization. Ameroid constrictors and hydraulic balloon occluders were placed on the left anterior descending coronary artery (LAD) of 23 dogs, and the left IMA was implanted in the LAD territory. Dogs were randomized to receive continuous infusions of acidic FGF with heparin, heparin alone, or placebo directly into the IMA for 8 wk. Regional myocardial blood flow was assessed in the conscious state 3 days and 8 wk after operation. Left ventricular function was determined in the anesthetized state at the 8-wk conclusion of treatment. In all dogs, IMA occlusion reduced mean maximal LAD zone perfusion by 28% (P < 0.001), without influencing regional contraction. When IMA occlusion was superimposed on left circumflex coronary artery (LCX) occlusion, LAD zone perfusion declined by 34% (relative to LCX occlusion alone), significantly impairing regional contraction. Treatment with either acidic FGF plus heparin or heparin alone improved IMA-derived collateral flow; however, addition of acidic FGF to heparin afforded no additional advantage over heparin by itself. We conclude that acidic FGF did not enhance myocardial angiogenesis in this model. IMA-derived collateral flow has significant functional importance; however, it is evident in the dog only when other sources of collateral flow are compromised.

Anastomosis, Surgical↗