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J C Stanley

Publications and source records attributed to J C Stanley.

At least 37 records · Page 2Linked to original sources
PubMed1998

Excessive oral amphetamine use as a possible cause of renal and splanchnic arterial aneurysms: a report of two cases.

INTRODUCTION: Multiple visceral aneurysms are uncommon and usually result from connective tissue diseases, systemic arteritis, or mycotic lesions. An association between multiple visceral aneurysms and excessive oral amphetamine use has not been reported. METHODS: The clinical features of 2 patients at the University of Michigan Medical Center for treatment of multiple visceral aneurysms and amphetamine use were reviewed. RESULTS: The patients had histories of excessive oral amphetamine use that ranged from 50 mg daily for 22 years to 200 mg daily for 2 years. No evidence was seen of systemic arteritis, connective tissue disorder, or an infectious process that may have caused the aneurysms. The arteriograms documented multiple splanchnic and renal artery aneurysms that involved both the large and the small arteries. The aneurysms of 1 patient were managed conservatively, and the patient has not had any clinical sequelae of the aneurysms during 14 years of follow-up. The second patient had hematobilia from a ruptured hepatic artery aneurysm that was treated with transcatheter embolic occlusion of the bleeding vessel. The patient had no recurrent gastrointestinal problems and continued to use amphetamines until his death from a cerebrovascular accident 6 years later. CONCLUSION: A possible association between excessive oral amphetamine use and multiple visceral aneurysms is reported for 2 patients in whom other risk factors were absent. The potential for chronic oral amphetamine use to cause multiple visceral aneurysms is an ill-defined but not unexpected complication of this substance that is known to contribute to arterial hypertension and to produce a form of necrotizing arteritis.

Administration, Oral↗
PubMed1998

Somatostatin gene transfer and expression in endothelial cells.

PURPOSE: The antiproliferative and antisecretory effects of somatostatin have many potential uses in the clinical setting. Retroviral gene transfer of somatostatin to endothelium is a potential means of local delivery of this peptide to specific vascular beds. This investigation was designed to determine whether transduced endothelial cells (ECs) could produce and post-translationally process somatostatin. METHODS: Cultured canine venous, rat aortic, and rat microvascular ECs were transfected with retroviruses containing a human somatostatin cDNA or a control beta-galactosidase gene. Total and isoform somatostatin production and uniformity of beta-galactosidase expression were analyzed, as were the effects of somatostatin production on EC proliferation. RESULTS: Somatostatin-transduced canine venous ECs, but not rat ECs, produced approximately 10 times as much total somatostatin as did control-transfected ECs (450 +/- 32 vs 49 +/- 10 pmol/L, p < 0.05). The predominant isoform of somatostatin produced was somatostatin-14. Production of somatostatin was stable with passage and did not impair the growth of canine ECs. The failure of rat ECs to produce somatostatin correlated with nonuniform expression of beta-galactosidase, suggesting that promoter silencing was responsible for failure of transgene expression. CONCLUSION: Retroviral gene transfer of somatostatin to canine ECs results in the production of physiologically relevant concentrations of biologically active somatostatin. Significant species differences exist in EC production of somatostatin, with promoter silencing being a potential mechanism of failure of gene expression. Gene therapy strategies using retroviral transfer of somatostatin to ECs may allow somatostatin delivery to focal areas of the vasculature.

Animals↗
PubMed1998

Prospective, randomized comparison of deep or superficial cervical plexus block for carotid endarterectomy surgery.

BACKGROUND: Carotid endarterectomy may be performed under cervical plexus block with local anesthetic supplementation by the surgeon as necessary during surgery. It is unclear, however, whether deep or superficial cervical plexus block offers the best operating conditions or patient satisfaction. Therefore, the authors compared the two in patients undergoing carotid endarterectomy. METHODS: Forty patients undergoing carotid endarterectomy were randomized to receive either a superficial or a deep cervical plexus block with 20 ml bupivacaine, 0.375%. Outcomes subjected to statistical analysis included supplemental anesthetic supplementation with lidocaine, 1%, by the surgeon, dermatomes affected by the block, paresthesia during block placement, postoperative pain scores, and analgesic requirements. RESULTS: Median supplemental lidocaine requirements were 6 ml (range, 0.5 to 20 ml) in the deep block group and 6 ml (range, 0 to 20 ml) in the superficial block group (P = 0.7323). Patients in the deep block group who reported paresthesia during block placement required less lidocaine supplementation (median, 2; range, 0.5 to 20 ml) than the 9.5 ml (range, 6 to 15.5 ml) required by those who did not experience paresthesia (P = 0.0113). Compared with patients in the superficial block group, those in the deep block group were less likely to need analgesia in the first 24 h after operation (P = 0.047), and those who required analgesia received it later (6.6 +/- 4.1 vs. 3.9 +/- 1.4 h after operation; Student's t test, P = 0.02). One patient in each group expressed dissatisfaction with the technique. CONCLUSIONS: Carotid endarterectomy may be performed satisfactorily during superficial or deep cervical plexus block placement with no differences in terms of supplemental local anesthetic requirements, although this is influenced by whether paresthesia is elicited during placement of the deep block. Therefore, the clinician's decision to use one block rather than another need not be based on any assumed superiority of one block based on intraoperative conditions or patient satisfaction.

Aged↗
PubMed1998

Renal anatomic changes on magnetic resonance imaging and gadolinium-enhanced magnetic resonance angiography after renal revascularization. Original investigation.

RATIONALE AND OBJECTIVES: The anatomic and hemodynamic renal changes after renal arterial revascularization (RAR) were investigated. METHODS: Thirty-seven kidneys and 40 renal arteries were evaluated in 20 patients by using magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) to assess pre- and post-RAR renal length and mass, parenchymal thickness, renal enhancement, renal artery caliber, poststenotic dilation, and signal dephasing on 3D phase contrast (PC). The kidneys and renal arteries were segregated into three groups. Group 1 included 16 patients who benefited from RAR (defined as clinical improvement based on decreased serum creatinine or fewer number of antihypertensive medications) in whom 26 renal arteries in 25 kidneys were studied. Intervention included renal artery endarterectomy (n = 20); aortorenal bypass (n = 3); renal artery reimplantation (n = 3); and percutaneous transluminal angioplasty (PTA; n = 1). A total of 27 interventions was performed, as PTA failed for one patient who subsequently underwent aortorenal bypass before reimaging. Group 2 included four patients who did not clinically benefit. A total of eight revascularized arteries were studied in seven kidneys. In group 3, six renal arteries in five kidneys from groups 1 and 2 without RAS/RAR were analyzed as an internal control. RESULTS: Technical success (defined as increased vessel caliber after intervention) was achieved in 33 of the 34 revascularized arteries. A statistically significant increase in renal length occurred regardless of clinical outcome (pre-RAR, 9.5 cm; post-RAR, 10.5 cm; P < 0.0001). Parenchymal thickness and renal mass, however, improved only in patients who benefited clinically from RAR. Parenchymal enhancement was unchanged in any of the groups studied. No significant morphologic changes were detected in the control group. CONCLUSIONS: Magnetic resonance imaging and Gd-MRA detect anatomic and hemodynamic changes that occur with renal revascularization.

Adult↗
PubMed1997

David M. Hume memorial lecture. Surgical treatment of renovascular hypertension.

BACKGROUND: Renal artery occlusive disease is the most common form of surgically correctable hypertension. Considerable scientific advances have improved our understanding of the pathophysiologic sequellae of a renal artery stenosis, the means of documenting the functional importance of such lesions, and the role of alternative surgical approaches in treating this disease. This work assesses the historical basis for the surgical treatment of renovascular hypertension. DATA SOURCES: A review of the American literature on the subject of renovascular hypertension was undertaken, with particular attention to early work emanating from the University of California, San Francisco, the University of Michigan, and Vanderbilt University. These three institutions had considerable influence on the evolving techniques of operative intervention for renovascular hypertension. CONCLUSIONS: The contemporary surgical management of renal artery stenotic disease causing secondary hypertension includes recognition of the heterogeneic character renal artery diseases, documentation of the functional significance of the stenoses, and performance of a properly chosen operation. Surgical therapy benefits 85% to 95% of properly selected patients having renovascular hypertension.

Fibrosis↗
PubMed1997

Differential effects of novel protamine variants on myocyte contractile function with left ventricular failure.

BACKGROUND: Protamine administration can cause left ventricular (LV) dysfunction, which may have clinical significance in the setting of congestive heart failure (CHF). Protamine variants have recently been constructed with heparin reversal capacity similar to protamine. The purpose of this study was to examine the potential differential effects of these protamine variants on isolated myocyte contractile function in normal myocytes and in myocytes after the development of CHF. METHODS: Contractile function was measured by means of computer-aided videomicroscopy in myocytes from five normal pigs and five pigs with CHF induced by rapid pacing (240 beats/min for 3 weeks). Myocyte contractility was examined in the presence of 40 micrograms/ml native protamine or one of three protamine variants: (1) reduced charge (+18) and lysine substituted for arginine; (2) lysine-substituted variant with glutamic acid substituted for the initial proline; or (3) arginine-rich peptide with a terminal arginine-glycine-aspartic acid (RGD) amino acid sequence. RESULTS: In the presence of native protamine, myocyte percent shortening fell from baseline in both the normal (2.86 +/- 0.15 versus 4.58 +/- 0.08, p < 0.05) and the CHF groups (1.01 +/- 0.06 versus 2.07 +/- 0.05, p < 0.05). With both of the lysine-substituted protamine variants, percent shortening fell from baseline in the normal group (3.42 +/- 0.20 for arginine and 3.74 +/- 0.20 for glutamic acid versus 4.58 +/- 0.08, p < 0.05), and was unchanged in the CHF group (1.94 +/- 0.13 versus 2.07 +/- 0.05, p = 0.34 for arginine; and 1.96 +/- 0.10 versus 2.07 +/- 0.05, p = 0.31, for glutamic acid). However, with the arginine/RGD variant, percent shortening fell from baseline in both the normal (2.86 +/- 0.23 versus 4.58 +/- 0.08, p < 0.05) and the CHF groups (1.32 +/- 0.10 versus 2.07 +/- 0.05, p < 0.05). CONCLUSIONS: Specific changes in the primary and secondary structures of protamine had different effects on myocyte contractile function. Furthermore, the negative effects of lysine-substituted protamine variants on myocyte contractility were less pronounced in both CHF and normal myocytes. Thus protamine variants may be of clinical use, particularly in the setting of preexisting LV dysfunction.

Animals↗
PubMed1997

A novel protamine variant reversal of heparin anticoagulation in human blood in vitro.

PURPOSE: Protamine reversal of heparin anticoagulation during cardiovascular surgery may cause severe hypotension and pulmonary hypertension. A novel protamine variant, [+18RGD], has been developed that effectively reverses heparin anticoagulation without toxicity in canine experiments. Heretofore, human studies have not been undertaken. This investigation hypothesized that [+18RGD] would effectively reverse heparin anticoagulation of human blood in vitro. METHODS: Fifty patients who underwent anticoagulation therapy during vascular surgery had blood sampled at baseline and 30 minutes after receiving heparin (150 IU/kg). Activated clotting times were used to define specific quantities of [+18RGD] or protamine necessary to completely reverse heparin anticoagulation in the blood sample of each patient. These defined amounts of [+18RGD] or protamine were then administered to the heparinized blood samples, and percent reversals of activated partial thromboplastin time, thrombin clotting time, and antifactor Xa/IIa levels were determined. In addition, platelet aggregation assays, as well as platelet and white blood cell counts were performed. RESULTS: [+18RGD] and protamine were equivalent in reversing heparin as assessed by thrombin clotting time, antifactor Xa, antifactor IIa levels, and white blood cell changes. [+18RGD], when compared with protamine, was superior in this regard, as assessed by activated partial thromboplastin time (94.5 +/- 1.0 vs 86.5 +/- 1.3% delta, respectively; p < 0.001) and platelet declines (-3.9 +/- 2.9 vs -12.8 +/- 3.4 per mm3, respectively; p = 0.048). Platelet aggregation was also decreased for [+18RGD] compared with protamine (23.6 +/- 1.5 vs 28.5 +/- 1.9%, respectively; p = 0.048). CONCLUSIONS: [+18RGD] was as effective as protamine for in vitro reversal of heparin anticoagulation by most coagulation assays, was statistically more effective at reversal than protamine by aPTT assay, and was associated with lesser platelet reductions than protamine. [+18RGD], if less toxic than protamine in human beings, would allow for effective clinical reversal of heparin anticoagulation.

Aged↗
PubMed1997

Vascular surgeons' resource use at a university hospital related to diagnostic-related group and source of admission.

PURPOSE: To determine whether differences in the conduct of individual practices of attending vascular surgeons account for variations in resource use at a university hospital. METHODS: The practice patterns of six attending vascular surgeons at the University of Michigan Hospital were assessed for patient length of stay (LOS), ancillary service use, and the number of nursing hours required. Included in the study were 1930 hospitalized patients who had one of the 10 most frequently encountered diagnostic related groups (DRGs). Statistical analyses of variables that were thought likely to affect resource use included multiple regression models. RESULTS: Patient age, sex, insurance, source of admission (direct admission or transfer admission), surgeon, and DRG category together accounted for 22% of LOS variation, 27.7% of variation in ancillary service use, and 29.4% of variation in nursing hours. In no model did the individual surgeon's practice significantly effect the LOS, ancillary use, or nursing hours. Patients transferred from other hospitals had increased resource use in all models. The DRG category alone explained 20.9% of the variance in LOS, 25.2% of the variation in ancillary service use, and 21.2% of the variance in nursing hours. CONCLUSION: Differences in the conduct of individual vascular surgeons' practices accounted for less than 1% variation in hospital resource use. The most important influences on resource use were the DRG category and the source of patient admission. Modification of the frequency and manner of accepting transfer patients to vascular surgery services of a university hospital may have a major impact on hospital resource use.

Diagnosis-Related Groups↗
PubMed1997

Transforming growth factor-beta 1 increases lysyl oxidase enzyme activity and mRNA in rat aortic smooth muscle cells.

PURPOSE: This investigation was designed to test the hypothesis that transforming growth factor-beta 1 (TGF-beta 1) regulates lysyl oxidase secretion from vascular smooth muscle cells. Lysyl oxidase is an enzyme that catalyzes an essential step in collagen and elastin cross-linking in the extracellular matrix, and TGF-beta 1 has been implicated in the pathogenesis of restenosis after vascular injury. The effect of TGF-beta 1 on lysyl oxidase in vascular smooth muscle cells has not been previously defined. METHODS: Rat aortic smooth muscle cells were grown in culture to confluence. Cells in passage 2 to 6 were incubated for 24 hours in media containing 0.1, 0.5, 1.0, or 10.0 ng/ml of TGF-beta 1. Lysyl oxidase activity in the media was quantitated with a tritium-release bioassay against an insoluble 3H-labeled aortic clastin substrate. Northern blot analyses were performed to determine steady-state levels of lysyl oxidase mRNA in the smooth muscle cells. RESULTS: Lysyl oxidase activity in the media increased 1.5-fold above control levels after exposure to 10 ng/ml of TGF-beta 1 (p < 0.01). This increase in lysyl oxidase activity was associated with a concentration-dependent increase in steady-state levels of lysyl oxidase mRNA, being 4.3- and 6.2-fold above control levels after exposure to 1 and 10 ng/ml TGF-beta 1, respectively (p < 0.01). The observed increase in steady-state lysyl oxidase mRNA after exposure to TGF-beta 1 was also time-dependent over the 24-hour experimental period. CONCLUSIONS: TGF-beta 1 appears to regulate lysyl oxidase in cultured rat aortic smooth muscle cells. Increases in lysyl oxidase activity may be one of the mechanisms by which TGF-beta 1 contributes to arterial restenosis after vascular injury.

Animals↗
PubMed1997

Gender differences in abdominal aortic aneurysm prevalence, treatment, and outcome.

PURPOSE: The purpose of this study was to investigate gender differences in the management of and outcome of surgery for abdominal aortic aneurysms (AAA). METHODS: Hospital discharge data from all acute care hospitals in Michigan, as compiled in the Michigan Inpatient Data Base, were retrospectively analyzed to assess sex differences in regard to AAA prevalence, treatment, and surgical outcome from 1980 to 1990. This population database included 11,512 women and 29,846 men 50 years of age and older with diagnoses of intact or ruptured AAA. RESULTS: Hospitalizations for intact or ruptured AAA were approximately five times more common among men compared with women. After controlling for age and year of surgery, men were 1.8 times as likely as women to have an intact AAA treated surgically and 1.4 times as likely to have a ruptured AAA treated surgically (95% confidence intervals, 1.7 to 1.9 and 1.2 to 1.7, respectively). Women who had operations for intact AAA had a 1.4 times greater risk of dying compared with men, and women who had operations for ruptured AAA had a 1.45 times greater risk of dying, after controlling for other predictors of death (95% confidence intervals, 1.14 to 1.73 and 1.10 to 1.90, respectively). CONCLUSIONS: In a population-based statewide experience, women who had intact or ruptured AAA were less likely than men to undergo aortic reconstruction and, when they did, were less likely than men to survive to discharge.

Aged↗
PubMed1997

Differential clinical workloads among faculty at a major academic health center.

OBJECTIVE: The authors analyzed patient care (1981-1995) and financial data (1991-1996) to determine if differential workloads existed at a major academic health center. SUMMARY BACKGROUND DATA: Academic health centers differ markedly from community-based medical centers, but they are required to compete with others who have a more circumscribed mission and a responsibility for providing less complex care. Changes in health care systems may lessen incentives to generate clinical revenue and may adversely affect educational and research programs. METHODS: Patient care data at the University of Michigan Health System were analyzed by discipline for level of activity from 1981 to 1995 and were compared to professional and institutional financial data from 1991 to 1995. RESULTS: Surgeons represented 11% of the total full-time physicians throughout the period of the study (94 of the 836 Medical Center physicians, 1995). They accounted for 33% of hospital admissions (11,616 of 35,101) and 16% of outpatient visits (92,364 of 568,738). Since 1981, surgeons experienced a 249% increase in total operative workload (6799-16,909 procedures), representing a 30% increase in operations/surgeon (138-180 operations). Surgical efforts in 1995 accounted for 29% of the total professional fee revenue and $240 million of the $512-million University of Michigan Hospital revenue. CONCLUSIONS: Surgeons had a greater collective and individual responsibility than did nonsurgeons for clinical activity and the financial viability of the academic health centers studied. Many proposals for financing health care delivery systems have the potential to exacerbate this differential. Restructuring of academic health centers must address this fact, lest their academic mission and scholarly activity be compromised.

Academic Medical Centers↗
PubMed1997

Dual cell cycle-specific mechanisms mediate the antimitogenic effects of nitric oxide in vascular smooth muscle cells.

OBJECTIVE: To determine the cell cycle specificity and intracellular mechanisms involved in inhibition by nitric oxide (NO) of vascular smooth muscle cell mitogenesis. METHODS: Cultured rat aortic smooth muscle cells were synchronized by serum withdrawal, treated with the NO donor S-nitroso-N-acetylpenicillamine and the cyclic GMP analog 8-Br-cGMP at various times during cell cycle progression, and DNA synthesis measured during the S phase. Two additional NO donors, 5-nitroso-glutathione and diethylamine NONOate, were used to confirm the inhibition of DNA synthesis by S-nitroso-N-acetylpenicillamine, and the ability of two antagonists of free NO to reverse the effects of NO donors was also evaluated. Bypass of ribonucleotide reductase by use of exogenous deoxynucleosides was attempted to determine whether inhibition of this S-phase enzyme was the mechanism by which NO inhibited DNA synthesis during the S phase. RESULTS: Vascular smooth muscle cell mitogenesis was inhibited by cyclic GMP (cGMP) up to late G1 phase of the cell cycle, which corresponded to the point of greatest sensitivity to exogenous NO. In contrast to cGMP, three different NO donors inhibited DNA synthesis when added to cells synchronized in S phase, beyond the restriction point of cell cycle control in late G1 phase. This S-phase inhibition was reversible by removal of the NO donor or addition of two NO antagonists and was not observed with non-NO analogs of the donors. Inhibition by NO donors in S phase was neither reversed by the guanylate cyclase inhibitor methylene blue nor mimicked by exogenous cGMP. The S-phase inhibition by all three NO donors was reversed partially by bypass of ribonucleotide reductase, establishing this enzyme as an S-phase target of NO. CONCLUSIONS: These findings demonstrate that NO inhibits smooth muscle mitogenesis by cGMP-dependent and -independent mechanisms acting at distinct points in the cell cycle. NO is the first endogenous substance to have been shown to inhibit mitogenesis beyond the restriction point in late G1 phase, suggesting that it plays a role in regulation of cells that have lost normal mechanisms of G1 growth control, such as the hyperproliferative smooth muscle cells noted in hypertension and restenosis.

Animals↗
PubMed1997

Hemodynamically significant atherosclerotic renal artery stenosis: MR angiographic features.

PURPOSE: To identify magnetic resonance (MR) angiographic features of hemodynamically significant renal artery stenosis. MATERIALS AND METHODS: Forty-seven patients underwent MR angiography of the renal arteries, including T1-weighted spin-echo and three-dimensional gadolinium-enhanced spoiled gradient-echo and three-dimensional phase-contrast pulse sequences, followed by renal revascularization. Thirty-five patients (52 arteries) were identified who benefited from renal revascularization, which indicated that they had hemodynamically significant renal artery stenoses. Kidney length, cortical thickness, parenchymal enhancement, and poststenotic dilatation were measured. Arteries were also examined for signal drop-out (dephasing) on phase-contrast angiograms; dephasing was considered severe if the stenotic artery appeared occluded on phase-contrast angiograms. RESULTS: Poststenotic dilatation of greater than 20% was present in 36 (59%) of 52 hemodynamically significant renal artery stenoses, and severe dephasing was present in 45 (87%) of 52. In patients with unilateral hemodynamically significant stenosis or occlusion, mean ischemic kidney length was reduced to 9.3 cm compared with 10.7 cm for the contralateral normal kidney (P = .009), mean parenchymal thickness was reduced (1.2 vs 1.7 cm; P < .001), and mean parenchymal enhancement was 15% less on the ischemic side (P = .05). Severe dephasing on phase-contrast angiograms was present in nine (75%) of 12 unilateral hemodynamically significant stenoses but in only one contralateral normal renal artery (P < .001). CONCLUSION: MR angiography depicts features of renal artery stenosis that are markers of hemodynamic significance.

Adult↗
PubMed1997

Cell cycle effects of nitric oxide on vascular smooth muscle cells.

We characterized the cell cycle block induced by nitric oxide (NO) on smooth muscle cells (SMC). We hypothesized that the inhibition of SMC proliferation by NO was due to a specific block in cell cycle progression. Treatment of cultured rat aortic SMC with the NO donors S-nitroso-N-acetylpenicillamine or S-nitrosoglutathione (0.1 mM for 48 h) resulted in a 50% decrease (P < 0.05) in the fraction of cells in the S and G2 + M phases and a corresponding increase in the G1 fraction, suggesting that NO inhibits entry into S phase, causing accumulation of cells in G1 phase. Application of both NO donors to cycling SMC resulted in a short-term, concentration-dependent (0.06-0.3 mM) inhibition of ongoing DNA synthesis as measured by radiothymidine incorporation, demonstrating that NO causes an S-phase arrest. The S-phase arrest by NO was not mimicked by exogenous guanosine 3',5'-cyclic monophosphate (cGMP, 10 mM) and was associated with, but not due to, a 20% inhibition of RNA synthesis. The S-phase block was completely reversed within 2 h of removal of the NO donors, similar to inhibition by the ribonucleotide reductase inhibitor hydroxyurea. Prolonged treatment of SMC with either NO donor (0.1 mM) did not synchronize cells at the G1-S boundary as expected after a prolonged S-phase arrest, but instead induced a quiescent G0-like state characterized by a 12- to 18-h lag before DNA synthesis returned to normal levels after NO removal. These findings demonstrate that NO inhibition of SMC proliferation is associated with two distinct and reversible cell cycle arrests, an immediate cGMP-independent S-phase block followed by a shift back in the cell cycle from the G1-S boundary to a quiescent G0-like state.

Animals↗
PubMed1997

Comparison of the hemodynamic and hematologic toxicity of a protamine variant after reversal of low-molecular-weight heparin anticoagulation in a canine model.

Using the dog as an animal model, we developed an experimental preparation to compare hemodynamic and hematologic toxicity of anticoagulation reversal. Currently, protamine sulfate reversal of standard unfractionated heparin and low-molecular-weight heparin (LMWH) anticoagulation causes adverse side effects, including decreased systemic mean arterial pressure (MAP), decreased cardiac output (CO), decreased oxygen consumption (VO2), and thrombocytopenia. In addition, standard protamine is only marginally effective at reversing the factor Xa inhibition induced by LMWHs. We have produced protamine-like variant peptides to decrease the adverse responses attributed to standard protamine. The hemodynamic, hematologic, and coagulation effects of standard protamine and the protamine variant (+18RGD) were assessed after reversal of LMWH anticoagulation in anesthetized dogs. Flow probes and vascular catheters were surgically implanted for measurement of hemodynamic parameters including MAP, CO, VO2, and heart rate (HR). Hematologic studies (platelet and white blood cell counts) and coagulation studies (activated clotting time [ACT], activated partial thromboplastin time [aPTT], thrombin clotting time [TCT], antifactor Xa and antifactor IIa values) also were performed. The protamine variant +18RGD was less toxic, induced less thrombocytopenia, and was more effective in anticoagulation reversal than was standard protamine sulfate. Results of this study indicate that the dog may be a useful model for investigating important hemodynamic, hematologic, and coagulation parameters during reversal of LMWH anticoagulation by use of synthetic protamine variants.

Animals↗
PubMed1997

The changing vascular surgery workforce.

An adequate workforce is requisite for efficient and quality surgical care of patients having vascular disease. Data from 1985 and 1992 United States workforce studies provide the basis for certain projections. Vascular surgeons performed 41% of vascular operations in 1985 and 51% in 1992. The basis for this change seems related to the fact that younger general surgeons are less likely to practice vascular surgery than retiring senior general surgeons, whom they are replacing, and vascular surgeons have assumed the care of patients usually treated by the latter group of surgeons. Our aging society compounds this change. Patients older than 65 years will exhibit a 73% increase from 2010 to 2030, with a subsequent greater need for more vascular operations, which are predicted to be 1,020,067 in 2020, compared with 583,000 in 1992. A larger workforce will be required to meet this need. Although innovative technology and changes in health care delivery may cause unpredictable changes in these anticipated workforce needs, the potential exists that there will be insufficient numbers of surgeons available to provide adequate surgical care early in the next century, unless changes occur in the training and practice of general and vascular surgeons.

Aged↗