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Biomedical subjects

M R Jackson

Publications and source records attributed to M R Jackson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Primary stenting of atherosclerotic renal artery ostial stenosis.

Percutaneous transluminal angioplasty for atherosclerotic ostial lesions of the renal arteries has resulted in high restenosis rates. Recent reports of angioplasty with intravascular stenting show improved results over angioplasty alone. The purpose of this study is to review the results of primary stenting of ostial renal artery stenosis at our institution. Twenty one patients (11 men, 10 women, age 63 +/- 11 years), with atherosclerotic renal artery ostial stenosis in association with hypertension or renal insufficiency underwent renal angioplasty with primary stenting during a 2-year period. Medical records were reviewed for indications, technical success, complications, restenosis, response of hypertension and response of renal insufficiency. A technical success was defined as a normal postprocedure arteriogram with no residual stenosis and no residual gradient. Restenosis was defined as > or =60% diameter reduction identified by arteriography, or duplex scan demonstrating a renal artery to aortic ratio of > or =3.5. Thirty-three stents were placed in 25 arteries with four patients having bilateral procedures. All patients were hypertensive. Nine patients (43%) had chronic renal insufficiency (creatinine > or =1.5 mg/dl). One patient was on hemodialysis. The immediate technical success rate was 95%. Six complications occurred in four patients (two pseudoaneurysms, two dissections requiring additional stents, renal failure, and atheroembolization). Mean arterial blood pressure improved from 117 +/- 13.4 to 103 +/- 12.8 mmHg (p = 0.002) after stenting. Serum creatinine levels decreased from 1.48 +/- 0.57 to 1.31 +/- 0.41 (p = 0.07). Eight patients developed restenosis. The mean follow up was 13 +/- 7 months. Life table analysis showed a cumulative restenosis rate of 65 +/- 18% at 24 months. We advise caution in the application of renal stenting for the treatment of ostial lesions, particularly in patients for whom standard surgical revascularization options are available.

Aged↗
PubMed1998

Determination of 60% or greater carotid stenosis: a prospective comparison of magnetic resonance angiography and duplex ultrasound with conventional angiography.

The morbidity and cost of conventional angiography (CA) have focused recent efforts in cerebrovascular imaging upon the exclusive use of noninvasive techniques. Our purpose was to prospectively evaluate carotid magnetic resonance angiography (MRA) and to compare its accuracy with color-flow duplex (CFD). Fifty patients were prospectively evaluated with CA and MRA after clinical and CFD findings indicated the need for carotid angiography. CFD measurements of peak systolic velocity (PSV) and end-diastolic velocity (EDV) were made. MRA results were categorized as 0%-39%, 40%-59%, 60%-79%, or 80%-99% stenosis or occluded. Determination of percent carotid stenosis by CA was made as in the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Using receiver operating characteristic (ROC) curves, the probability of correctly predicting a > or =60% stenosis using various CFD thresholds and MRA was assessed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in determining > or =60% stenosis were estimated. For MRA the sensitivity was 85% (95% Confidence Interval [CI] = 69%-94%), specificity 70% (CI = 56%-81 %), PPV 68% (CI = 53%-80%), and NPV 86% (CI = 72%-94%). For CFD the sensitivity was 89% (CI = 74%-96%), specificity 93% (CI = 82%-98%), PPV 89% (CI = 74%-96%), and NPV 93% (CI = 82%-98%). When MRA and CFD results were concordant (n = 64), the sensitivity was 100% (CI = 89%-100%), specificity 95% (CI = 81%-99%), PPV 94% (CI = 77%-99%), and the NPV was 100% (CI = 92%-100%). The area under the ROC curve for CFD was 95%, compared to 83% for MRA (p = 0.0005). We conclude that the low specificity of MRA precludes its use as the definitive imaging modality for carotid stenosis. The 93% specificity of CFD alone warrants its consideration as a definitive carotid imaging study. By ROC curve analysis, CFD offers superior accuracy to MRA. Our data support noninvasive preoperative carotid imaging for detecting a threshold stenosis of > or =60% whether CFD is used alone, or in combination with the selective use of MRA.

Aged↗
PubMed1998

Gastrointestinal complications after aortic surgery.

BACKGROUND AND PURPOSE: A major gastrointestinal complication (GIC) after aortic surgery may be disastrous, but these complications have received scant attention. This study was performed to determine the risk factors, associated events, and outcomes for patients with GIC. METHODS: We performed a secondary analysis of a prospective study that examined 120 consecutive patients who underwent transperitoneal aortic revascularization for aneurysmal or occlusive disease. RESULTS: The following 29 GICs developed in 25 patients (21%) within 30 days of aortic surgery: paralytic ileus that required replacement of nasogastric tubes (n = 12), upper gastrointestinal bleeding (n = 5), Clostridium difficile enterocolitis (n = 5), acute cholecystitis (n = 2), mechanical obstruction (n = 2), ascites (n = 2), and colon ischemia (n = 1). Seven patients required operations for GICs after aortic revascularization. A comparison of patients with and without GICs showed no differences in the prevalence of risk factors, presence of mesenteric artery stenoses, coexisting medical illnesses, antecedent gastrointestinal history, operative indication, preoperative fluid administration, or duration of operation. However, patients with GICs had more intraoperative complications (P = .004), greater intraoperative blood loss (P = .02), and more fluids during the postoperative period (P = .008). The mean duration of mechanical ventilation was 71 +/- 23 hours for patients with GICs versus 7 +/- 2 hours for patients without GICs (P = .006). A higher prevalence of pulmonary (P = .004) and renal (P = .001) complications was seen in the patients with GICs. The mean stay in the intensive care unit was 16 +/- 2 days for patients with GICs as compared with 5 +/- 0.4 days for patients without GICs (P < .001). Four deaths occurred, all caused by multisystem organ failure: 3 patients had GICs, and 1 did not have a GIC (P = .007). CONCLUSIONS: These results show that GICs are prevalent in transperitoneal aortic surgery and are associated with severe morbidity rates, increased hospital costs because of prolonged stay, and increased mortality rates. Some GICs appear to be associated with intraoperative events that lead to visceral hypoperfusion, and others can be attributed to mechanical causes. However, none of the variables examined in this study were predictive of GICs. In all, GICs should be considered serious adverse sequela after aortic revascularization. Because no risk factors for GICs have been identified, these complications currently cannot be prevented.

Acute Disease↗
PubMed1998

The incidence of heparin-induced antibodies in patients undergoing vascular surgery: a prospective study.

PURPOSE: This study prospectively assessed the incidence of heparin-induced antibodies in patients undergoing peripheral vascular surgery and determined whether the incidence is influenced by previous heparin exposure. METHODS: Fifty-four hospitalized patients (36 men and 18 women) undergoing peripheral vascular surgery and receiving intraoperative heparin anticoagulation were studied. Unfractionated porcine heparin was given for intraoperative anticoagulation and was not continued postoperatively. Carotid endarterectomy was performed in 36 patients, aortic reconstruction in 11 patients, and infrainguinal bypass in 7 patients. Plasma was tested before and after (14 +/- 7.5 [SD] days) surgery for IgG antibodies to the complex of heparin/platelet factor 4, using a standardized, validated enzyme-linked immunosorbent assay (ELISA). Results are expressed as an optical density ratio (ODR) of patient plasma to normal plasma, with the threshold for a positive result of > or = 1.8. Platelet counts and clinical outcomes were also assessed. RESULTS: The mean patient age was 67.2 +/- 9.7 years. A prior exposure to heparin was documented in 41% of patients. The mean intraoperative heparin dose was 9089 +/- 3607 units. Only 1 patient converted from a negative antibody status to a positive status (1.9%, 95% CI = 0.10%-11.18%). The change in the ELISA ODR after surgery was not significantly different for patients with (+0.042 +/- 0.272) and without (-0.022 +/- 0.299, P = 0.57) prior heparin exposure. Postoperatively, the platelet counts dropped from 227,620 +/- 78,308 microL, to 185,706 +/- 80,842 microL (P < .001). The decrease in platelet count was the same in patients with prior heparin exposure (-23.0 +/- 18.0%) and without (-18.0 +/- 14.0%, P = .46). One thrombotic complication occurred, a femorotibial bypass graft occlusion in a patient who tested negative for antibodies. CONCLUSION: Heparin-induced antibodies occur infrequently after peripheral vascular surgery. The commonly observed, mild degree of postoperative thrombocytopenia does not appear to be caused by heparin-induced antibodies. These results indicate that a standard dose of heparin for intraoperative anticoagulation during vascular surgery is not associated with a significant risk of heparin-induced thrombocytopenia and thrombosis.

Aged↗
PubMed1998

Biomagnetic isolation of antigen-specific CD8+ T cells usable in immunotherapy.

Isolating antigen-specific T lymphocytes is hampered by the low frequency of the cells and the low affinity between T-cell receptors (TCR) and antigen. We describe the isolation and purification of antigen-specific CD8+ T lymphocytes from mixed T-cell populations. Magnetic beads coated with major histocompatibility complex class I molecules loaded with specific peptide were used as a substrate for T-cell capture. Low-frequency T cells, as well as T cells with TCR of low affinity for the antigen were captured on the beads. Following isolation and expansion, recovered cells specifically killed target cells in vitro, and displayed antiviral effect in vivo.

Animals↗
PubMed1998

Application of an artificial neural network to predict specific class I MHC binding peptide sequences.

Computational methods were used to predict the sequences of peptides that bind to the MHC class I molecule, K(b). The rules for predicting binding sequences, which are limited, are based on preferences for certain amino acids in certain positions of the peptide. It is apparent though, that binding can be influenced by the amino acids in all of the positions of the peptide. An artificial neural network (ANN) has the ability to simultaneously analyze the influence of all of the amino acids of the peptide and thus may improve binding predictions. ANNs were compared to statistically analyzed peptides for their abilities to predict the sequences of K(b) binding peptides. ANN systems were trained on a library of binding and nonbinding peptide sequences from a phage display library. Statistical and ANN methods identified strong binding peptides with preferred amino acids. ANNs detected more subtle binding preferences, enabling them to predict medium binding peptides. The ability to predict class I MHC molecule binding peptides is useful for immunolological therapies involving cytotoxic-T cells.

Amino Acids↗
PubMed1998

Hemostatic efficacy of a fibrin sealant dressing in an animal model of kidney injury.

OBJECTIVE: The purpose of this study is to determine the hemostatic efficacy of a fibrin sealant dressing compared with a standard collagen control dressing in an animal model of kidney injury. METHODS: Twenty adult male Sprague-Dawley rats were administered general anesthesia and underwent partial nephrectomy with heparin anticoagulation (300 U/kg intravenous). Treatment of the cut surface of the kidney was randomized to three groups: group I, no hemostatic agent; group II, collagen dressing; and group III, fibrin sealant dressing. RESULTS: Blood loss was significantly less in group III (3.39+/-0.63 mL) than in group I (8.64+/-2.26 mL) and group II (8.63+/-1.72 mL; p < 0.001). The percentage decrease in the mean arterial pressure was significantly less in group III (34.09+/-15.58%) than in group I (59.66+/-16.19%) and group II (60.35+/-15.66%; p=0.015). CONCLUSION: Fibrin sealant dressings provide effective hemostasis and are superior to collagen dressings in an animal model of kidney injury. Additional development of fibrin sealant dressings for potential clinical use is warranted.

Animals↗
PubMed1998

Probing the activation requirements for naive CD8+ T cells with Drosophila cell transfectants as antigen presenting cells.

Activation of T cells involves multiple receptor-ligand interactions between T cells and antigen presenting cells (APC). At least two signals are required for T-cell activation: Signal 1 results from recognition of MHC/peptide complexes on the APC by cell surface T-cell receptors (TCR), whereas Signal 2 is induced by the interactions of co-stimulatory molecules on APC with their complementary receptors on T cells. This review focuses on our attempts to understand these various signals in a model system involving the 2C TCR. The structural basis of Signal 1 was investigated by determining the crystal structure of 2C TCR alone and in complex with MHC/peptide. Analysis of these structures has provided some basic rules for how TCR and MHC/peptide interact; however, the critical question of how this interaction transduces Signal 1 to T cells remains unclear. The effects of Signal 1 and Signal 2 on T-cell activation were examined with naive T cells from the 2C TCR transgenic mice, defined peptides as antigen and transfected Drosophila cells as APC. The results suggest that, except under extreme conditions, Signal 1 alone is unable to activate naive CD8 T cells despite the induction of marked TCR downregulation. Either B7 or intercellular adhesion molecule (ICAM)-1 can provide the second signal for CD8 T-cell activation. However, especially at low MHC/peptide densities, optimal activation and differentiation of CD8 T cells required interaction with both B7 and ICAM-1 on the same APC. Thus, the data suggest that at least two qualitatively different co-stimulation signals are required for full activation of CD8 T cells under physiological conditions.

Animals↗
PubMed1998

Diagnosis and management of venous thrombosis in the surgical patient.

Deep venous thrombosis (DVT) continues to be a source of major morbidity and mortality for surgical patients. The incidence of postoperative DVT is as high as 28% in some series. Risk factors include immobility, venous endothelial injury, stasis, and advanced age, all of which are highly prevalent in many populations of surgical patients. Diagnosis is generally confirmed by using duplex ultrasound to examine the legs. This modality has largely replaced contrast venography as the gold standard imaging test for DVT. Treatment begins with heparin and warfarin. Recently, low-molecular-weight heparin (LMWH) has been shown to be a suitable alternative to conventional, unfractionated heparin as the initial anticoagulant treatment of DVT. This change permits outpatient treatment of DVT in suitable patients. However, anticoagulation is contraindicated in many postoperative patients, who may then require an inferior vena caval filter. Iliofemoral venous thrombectomy should be considered when postoperative patients present with phlegmasia cerulea dolens. Long-term management of these patients focuses on measures to prevent clinical manifestations of chronic venous insufficiency.

Anticoagulants↗
PubMed1997

Major histocompatibility complex class II-dependent unfolding, transport, and degradation of endogenous proteins.

We have analyzed the ability of major histocompatibility (MHC) class II molecules to capture proteins in the biosynthetic pathway and whether this may be associated with MHC class II-dependent antigen processing. When coexpressed with HLA-DR 4 molecules in HeLa cells, influenza hemagglutinin was inhibited from folding and trimerization in the biosynthetic pathway, targeted to endosomal compartments, and rapidly degraded. Due to the interaction with MHC class II molecules, therefore, unfolded forms of hemagglutinin were bypassing the quality control mechanism of the secretory pathway. More important, however, the transport, endocytosis, and rapid degradation of unfolded hemagglutinin in the presence of MHC class II molecules suggest that proteins captured in the endoplasmic reticulum by class II molecules may become substrates for antigen processing and presentation to CD4-positive T cells. In insect cells we show that this phenomenon is not restricted to a few proteins such as hemagglutinin. A highly heterogeneous mixture of proteins from the endoplasmic reticulum including coexpressed hemagglutinin can form stable complexes with soluble HLA-DR alpha and beta chains that were transported into the supernatant. This mechanism may gain biological significance in abnormal situations associated with accumulation of unfolded or malfolded proteins in the endoplasmic reticulum, for example during viral infections.

Biological Transport↗
PubMed1997

Peptide-independent recognition by alloreactive cytotoxic T lymphocytes (CTL).

We have isolated several H-2K(b)-alloreactive cytotoxic T cell clones and analyzed their reactivity for several forms of H-2K(b). These cytotoxic T lymphocytes (CTL) were elicited by priming with a skin graft followed by in vitro stimulation using stimulator cells that express an H-2K(b) molecule unable to bind CD8. In contrast to most alloreactive T cells, these CTL were able to recognize H-2K(b) on the surface of the antigen processing defective cell lines RMA-S and T2. Furthermore, this reactivity was not increased by the addition of an extract containing peptides from C57BL/6 (H-2(b)) spleen cells, nor was the reactivity decreased by treating the target cells with acid to remove peptides bound to MHC molecules. The CTL were also capable of recognizing targets expressing the mutant H-2K(bm8) molecule. These findings suggested that the clones recognized determinants on H-2K(b) that were independent of peptide. Further evidence for this hypothesis was provided by experiments in which H-2K(b) produced in Drosophila melanogaster cells and immobilized on the surface of a tissue culture plate was able to stimulate hybridomas derived from these alloreactive T cells. Precursor frequency analysis demonstrated that skin graft priming, whether with skin expressing the wild-type or the mutant H-2K(b) molecule, is a strong stimulus to elicit peptide-independent CTL. Moreover, reconstitution experiments demonstrated that the peptide-independent CTL clones were capable of mediating rapid and complete rejection of H-2-incompatible skin grafts. These findings provide evidence that not all allorecognition is peptide dependent.

Animals↗
PubMed1997

Requirements for peptide-induced T cell receptor downregulation on naive CD8+ T cells.

The requirements for inducing downregulation of alpha/beta T cell receptor (TCR) molecules on naive major histocompatibility complex class I-restricted T cells was investigated with 2C TCR transgenic mice and defined peptides as antigen. Confirming previous results, activation of 2C T cells in response to specific peptides required CD8 expression on the responder cells and was heavily dependent upon costimulation provided by either B7-1 or ICAM-1 on antigen-presenting cells (APC). These stringent requirements did not apply to TCR downregulation. Thus, TCR downregulation seemed to depend solely on TCR/peptide/interaction and did not require either CD8 or B7-1 expression; ICAM-1 potentiated TCR downregulation, but only with limiting doses of peptides. TCR downregulation was most prominent with high affinity peptides and appeared to be neither obligatory nor sufficient for T cell activation. In marked contrast to T cell activation, TCR downregulation was resistant to various metabolic inhibitors. The biological significance of TCR downregulation is unclear, but could be a device for protecting T cells against excessive signaling.

Animals↗
PubMed1997

Saphenous vein versus polytetrafluoroethylene carotid patch angioplasty.

BACKGROUND: The optimal material for carotid patch angioplasty after endarterectomy remains uncertain. This study compares the early outcome and recurrent stenosis rates between saphenous vein (SV) and expanded polytetrafluoroethylene (ePTFE) carotid patch angioplasty. METHODS: The results of 421 consecutive carotid endarterectomies performed over a 72-month period were reviewed. Postoperative complications and restenosis rates, defined as > OR = 60% narrowing measured by color flow duplex, were compared. RESULTS: Patch angioplasty was performed with SV in 287 and with ePTFE in 110 cases. Patients who had undergone primary closure (n = 20) or whose form of closure was unknown (n = 4) were excluded. The mean age of patients and length of follow-up was similar between groups. Women were more likely to be patched with ePTFE than were men (36% versus 23%, P = 0.02). One death occurred in each group (0.3% SV, 0.9% ePTFE, P = 0.47), and four strokes occurred in each group (1.4% SV, 3.6% ePTFE, P = 0.22). Cervical hematomas requiring operative evacuation occurred in five SV closures and in three ePTFE closures (1.7% versus 2.7%, P = 0.69). Vein harvest site complications occurred in 6 patients (2%) who had undergone SV patch angioplasty. Recurrent stenosis occurred in 3 patients with SV closure and in 3 patients with ePTFE closure (1.0% versus 2.7%, P = 0.35). The 60-month restenosis rates by life table analysis were 2.6% +/- 2.1% for SV and 10.7% +/- 7.9% for ePTFE (P = 0.17). CONCLUSIONS: The incidence of postoperative complications is similar with SV or ePTFE patch angioplasty; however, vein harvest site complications are avoided with the use of ePTFE. Recurrent stenosis at 5 years occurs infrequently with either SV or ePTFE.

Aged↗
PubMed1997

Heparinoid anticoagulation and topical fibrin sealant in heparin-induced thrombocytopenia.

The development of heparin-induced thrombocytopenia in patients who require systemic anticoagulation for cardiac and vascular operations poses a therapeutic dilemma because no alternative anticoagulants are generally available. Heparinoid (Org 10172) has been used as an alternative anticoagulant under protocol or on a compassionate use basis, and has recently been approved by the Food and Drug Administration. There is, however, no heparinoid antagonist to reverse the anticoagulation. This report describes the combined use of heparinoid anticoagulation and adjunctive fibrin sealant for topical hemostasis in a patient with heparin-induced thrombocytopenia. Recommendations for perioperative monitoring of heparinoid anticoagulation are provided.

Anticoagulants↗
PubMed1997

Diagnosis of heparin-induced thrombocytopenia in the vascular surgery patient.

BACKGROUND: Recent studies have shown that patients with heparin-induced thrombocytopenia (HIT) form immunoglobulin G (IgG) and/or IgM antibodies directed against a complex of platelet factor 4 (PF4) and heparin. This recognition has resulted in the development of enzyme-linked immunosorbent assays (ELISAs) that use the heparin/PF4 complex as the antigen. This study describes the use of a standardized ELISA to assess antibody formation in five patients suspected of having HIT. METHODS: Five patients received heparin for treatment of arterial or venous thrombotic disorders. All patients had the ELISA performed to detect IgG or IgM antibodies directed against heparin-PF4, as well as the 14C serotonin release assay, when HIT was clinically suspected. RESULTS: HIT was diagnosed in four patients and ruled out in a fifth by using the ELISA. All patients had a 40% decrease in platelet count that returned to normal after heparin cessation. Only one of the four patients who tested positive by ELISA for IgG antibodies also tested positive by the 14C serotonin release assay. Treatment was significantly altered by the ELISA results in all five patients. CONCLUSIONS: It is likely that the ELISA is more sensitive in the diagnosis of HIT than the more traditional aggregation tests, and it may emerge as a new gold standard. Prospective studies in which serial laboratory testing is combined with measurement of clinical outcomes are needed and will eventually provide a greater understanding of the full spectrum of HIT and the clinical settings that precipitate thrombosis in the vascular surgery patient.

Adult↗
PubMed1997

Presentation and management of venous aneurysms.

PURPOSE: Venous aneurysms have been reported to occur in most major veins. These aneurysms may be misdiagnosed as soft tissue masses or as inguinal or femoral hernias. Venous aneurysms of the deep system have been associated with deep venous thrombosis (DVT) and pulmonary embolism (PE). To more precisely characterize these lesions, we reviewed our experience with the disease. METHODS: A retrospective analysis of our experience over 22 years was performed. The presentation and management of these lesions were reviewed and compared with the literature. RESULTS: Thirty-nine venous aneurysms were reported in 30 patients. There were 14 men and 16 women. The patients' ages ranged from 3 to 75 years. Thirty aneurysms were located in the lower extremities, four in the upper extremity, and five in the internal jugular vein. Fifty-seven percent of lower extremity aneurysms occurred in the deep system. Patients' symptoms were a mass (75%) associated with pain (67%) and swelling (42%). Thromboembolism occurred in six patients, DVT in three, and PE in three. Eight of nine patients (89%) who had aneurysms of the superficial venous system had their condition misdiagnosed. Diagnosis was made by phlebography (60%), color flow duplex scanning (27%), continuous-wave Doppler scanning (10%), or magnetic resonance imaging (10%). The aneurysm size ranged from 1.7 to 6.0 cm. Management consisted of tangential excision in five (17%), total excision in 23 (77%), and observation in seven (6%). CONCLUSIONS: Venous aneurysms are unusual vascular malformations that occur equally between the sexes and are seen at any age. Most patients have a painful mass of the extremity, and diagnosis is achieved by radiologic examination. Superficial venous aneurysms of the inguinal region are often misdiagnosed. Thromboembolism is more common in aneurysms involving the deep venous system. Because of their potential morbidity, management should be surgical in the majority of cases.

Adolescent↗