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Biomedical subjects

C B Anderson

Publications and source records attributed to C B Anderson.

At least 73 records · Page 4Linked to original sources

Combined arachidonic acid and ADP platelet inhibition maximizes patency of small-diameter vascular grafts.

Arachidonic acid (AA) and adenosine diphosphate (ADP) are potent stimuli of platelet aggregation. Each agonist may act through separate platelet pathways. In order to evaluate inhibition of ADP and AA on platelet aggregation, we studied the effect of ticlopidine (TC) and aspirin (ASA) alone and in combination on plasma thromboxane levels, platelet deposition, and patency of small-diameter vascular grafts in a canine model. Thirty-four mongrel dogs were classified as thrombosis prone (TP) or thrombosis resistant (TR) on the basis of in vitro platelet aggregation to AA. Four groups were studied: group I, control; group II, TC (100 mg/kg/day); group III, ASA (3 mg/kg/day); and group IV, TC/ASA (same doses). PTFE grafts were implanted bilaterally in the carotid and femoral arteries Ticlopidine inhibited in vitro platelet aggregation to both ADP and AA but had no significant effect on plasma thromboxane (Tx) B2 production. Aspirin inhibited AA-induced platelet aggregation and significantly decreased TxB2 production. Aspirin inhibited AA-induced platelet aggregation and significantly decreased TxB2 levels in both TP and TR animals (p less than 0.01). Although TC and ASA significantly inhibited platelet deposition and improved 1-month patency in both TP and TR animals, maximal patency was achieved in the group in which TC and ASA were combined. We conclude that platelet ADP and AA pathways are important determinants of the thrombogenic potential in vascular graft performance in dogs and that combined inhibition of both pathways achieves maximal vascular graft patency.

Adenosine Diphosphate↗

Prolonged survival in a child with renovascular hypertension from abdominal-pulmonary Takayasu's arteritis.

Takayasu's disease is an inflammatory condition of the large arteries which comprises circulation to the head, extremities, and, less often, the abdominal viscera or lungs. A 10-year-old girl with renovascular hypertension secondary to Takayasu's arteritis has been followed for over 5 years. Her course is unusual in that (1) her disease is not related to tuberculosis; and (2) despite a persistently active disease course, she has been allowed to experience a fairly normal life-style through continued, extensive medical and surgical management. Vascular involvement has been documented by digital subtraction angiography; less invasive techniques were not useful for monitoring disease progression.

Child↗

A newly identified surface coat on cochlear hair cells.

Routine electron microscope methods do not well preserve or stain the surface coat or glycocalyx on cochlear hair cells. In other tissues, enhanced preservation and staining of these glycoconjugates was obtained following fixation with glutaraldehyde containing a cationic dye (e.g., Alcian blue and ruthenium red). When cochleas were fixed with glutaraldehyde containing Alcian blue, the endolymphatic surface of hair cells, but not the supporting cells, displayed an extensive (approximately 90 nm thick) surface coat. Alcian blue positive material was also observed in the tectorial and basilar membranes and in a portion of the spiral ligament. In addition, acellular bands of Alcian blue positive material were observed between the tectorial membrane and the reticular lamina or inner sulcus cells. Although the function of these cochlear glycoconjugates is not yet known, it is proposed that they serve to attach the tectorial membrane to the organ of Corti, and they are involved in stereocilia fusion following sound exposure and ototoxic drug administration.

Animals↗

Comparison between the transabdominal and retroperitoneal approach for reconstruction of the infrarenal abdominal aorta.

To evaluate the efficacy of the retroperitoneal approach (RP) when compared with the transperitoneal (TP) approach in elective aortoiliac reconstruction, 104 consecutive cases were reviewed. From June 1983 through December 1985, 50 patients underwent aortoiliac reconstruction (26 for aortoiliac occlusive disease [AIOD] and 20 for abdominal aortic aneurysm [AAA]) through the TP approach and 54 patients underwent operation (30 for AIOD and 24 for AAA) through the RP approach. Both groups had similar revascularization procedures, associated diseases, and preoperative cardiac and pulmonary function parameters. The TP approach was associated with a larger intraoperative blood loss (1950 +/- 196 ml) when compared with the RP approach (1296 +/- 109 ml) (p less than 0.001). The intraoperative crystalloid requirements were also significantly higher for the TP approach (5994 +/- 296 ml) when compared with the RP approach (4455 +/- 295 ml) (p less than 0.0005). Similarly, the intraoperative blood requirements were higher for the TP approach (1235 +/- 115 ml) than the RP approach (853 +/- 61 ml) (p less than 0.001). Both groups had similar operative times. Nasogastric intubation and initiation of oral feeding was significantly prolonged in the TP group when compared with the RP group (p less than 0.001). Postoperative hospitalization was also considerably prolonged in the TP group when compared with the RP group (p less than 0.02). This experience demonstrates that the RP approach is a preferable alternative to the TP route in elective aortoiliac reconstruction.

Aged↗

Arachidonate lipoxygenase products and renal allograft rejection in dogs.

The production of 12-hydroxyeicosatetraenoic acid (12-HETE) and leukotriene B4 (LTB4) was studied in renal tissue obtained from renal allografts and normal kidneys of nonimmunosuppressed dogs that had undergone unilateral renal allotransplantation. We have shown that allografted renal cortex undergoing rejection synthesizes significantly greater quantities of 12-HETE than normal or autotransplanted control renal cortex. There was no significant increase in 12-HETE production by allografted medulla undergoing rejection. Production of LTB4 was significantly greater in the rejecting renal cortex compared to control renal cortex but was not different in the rejecting compared to normal renal medulla. Production of 12-HETE and LTB4 was significantly inhibited by the lipoxygenase-cyclooxygenase inhibitor BW755C, suggesting that production of these compounds was enzyme catalyzed. Histologic examination of renal tissue undergoing rejecting revealed varying degrees of tissue destruction and cellular infiltration. These histologic parameters correlated with the magnitude of 12-HETE production in the allografts. Our findings therefore indicate that arachidonate lipoxygenase products are generated in increased amounts by renal cortical tissue undergoing rejection and suggest that these products may be involved in the rejection process.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Initial characterization of humoral IL-2 response inhibition following donor-specific transfusions under azathioprine immunosuppression.

A previous study indicated that noncompetitive humoral inhibition of IL-2-induced proliferation was a frequent consequence of donor-specific transfusions under azathioprine immunosuppression. In this report, we present our initial characterization of the mode of action and nature of this humoral activity. A direct role for azathioprine seems unlikely since its removal from post-DST+A sera did not eliminate inhibition, nor did addition of azathioprine to normal sera mimic the inhibition by post-DST+A sera. Inhibition of the proliferative response to IL-2 was observed on an individual cell basis after IL-2 stimulation that did not involve a direct effect on DNA synthesis. Inhibition appeared to require optimal IL-2 receptor expression as well as optimal doses of IL-2, suggesting that inhibition is manifested at the postreceptor level. Inhibition could not be removed by reconstitution with normal sera, indicating that post-DST+A sera were not deficient in a nominal serum component, which is necessary for optimal proliferation. The inhibitory activity in post-DST+A sera was sensitive to chemical reduction and heat. Inhibition of the response to IL-2 was readily demonstrated using IL-2 responsive human or murine T lymphocytes. However, post-DST+A serum also inhibited proliferation of one of two IL-2 independent cell lines. These results suggest that the inhibitory activity in post-DST+A plasma/serum may be due to the induction of an inhibitor of cell proliferation that is either lacking or "deficient" in normal serum.

Antibody Formation↗

Preoperative immunomodulation of renal allograft recipients by concomitant immunosuppression and donor-specific transfusions.

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 113 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor/recipient combinations were at least 1-haplotype disparate and 17 were 2-haplotype disparate. Presensitization, defined as a positive Amos or antiglobulin T cell CM or a positive high-titer (greater than or equal to 1:8) B cell CM was present in 10 patients and not present in 103 patients. Attempts at desensitization of the already sensitized group were uniformly unsuccessful. Treatment of the 103 nonpresensitized patients resulted in transient sensitization in 3 patients, permanent sensitization in 8, and no evidence of sensitization in 92. Ninety-one nonsensitized patients underwent renal transplantation from the specific blood donor, and only 5 have experienced renal allograft rejection loss during a mean follow-up period of 26 months (6 to 70 months). Fifty-four percent have never experienced a rejection episode. The allograft survival rate at 2 years (91%) and 5 years (89%) is significantly better (P less than .01) than our historical experience with 1-haplotype living-related transplants at 2 years (66%) and 5 years (64%). The low rate of sensitization (8%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of rejection (5%) argues for a modification of the immunologic response rather than a selecting out process as the mechanism for improved allograft survival.

Azathioprine↗

Alcian blue staining of cochlear hair cell stereocilia and other cochlear tissues.

Using whole-mount surface preparations of the chinchilla organ of Corti, the anionic characteristics of cochlear tissues was investigated with the polycationic dye Alcian Blue. Our primary goal was to specifically stain the hair cell stereocilia for the purpose of producing cytocochleograms. To specifically stain hair cell stereocilia we investigated the effects of different fixatives and the 'critical electrolyte concentration' [Scott and Dorling (1965) Histochemie 5, 221-233] of MgCl2 on staining specificity. The stereocilia and the tectorial membrane were the most intensely stained cochlear structures and presumably have a strong negative charge. The most important factor in producing specific staining was fixation in osmium tetroxide rather than the addition of an electrolyte to the Alcian Blue staining solution. The use of Alcian Blue produced intense staining of hair cell stereocilia against an unstained background using standard, brightfield light microscopy.

Alcian Blue↗

Prediction of crossmatch outcome in highly sensitized dialysis patients based on the identification of serum HLA antibodies.

High levels of allosensitization (greater than 50%), which often occur in dialysis patients awaiting renal transplant, make donor selection difficult. Such patients may be included in elaborate protocols in which they are crossmatched with all available ABO compatible donors, or crossmatching may be deferred until a very-well-matched donor becomes available. The former approach of random crossmatching is costly and inefficient, while the latter approach may overlook crossmatch-compatible donors. We believe that the identification of antibodies present in highly reactive sera and the use of this information in donor selection would increase the frequency of crossmatch-negative donors for these patients. In this study eleven sera, reactive with 70% to 100% of a random cell panel, were obtained from multiply transfused dialysis patients. Sera were analyzed by standard (CDC) and antiglobulin augmented (AHG-CDC) lymphocytotoxicity, and by differential absorption with HLA-typed platelets. All sera contained only one or two antibodies directed against the high frequency public HLA epitopes, accounting for 85% to 100% of each serum's total reactivity. These characterized sera were crossmatched with 114 random normal donors. The frequency of negative crossmatches was 20.5%. However, if the serum antibody data had been used to preselect donors for crossmatch--that is, to exclude donors that were likely to be positive--the negative crossmatch frequency would have increased to 86.4%. The use of the serum analysis data in donor selection would have reduced the total number of required crossmatches by 78%. Serum analysis correctly predicted the outcome of 95.6% of crossmatches performed with an average of 3% false positives and 1.3% false negatives. This approach to donor selection reduces unnecessary crossmatching and increases the likelihood of finding crossmatch-compatible donors for highly reactive patients.

ABO Blood-Group System↗

Modulation of the response to interleukin 2 in recipients of donor-specific transfusions under azathioprine immunosuppression.

The effect of plasma from recipients of donor-specific transfusions given under azathioprine immunosuppression (DST+A) on the response to IL-2 was examined. Pre-DST+A plasma markedly enhanced the proliferative response to suboptimal doses of IL-2 by IL-2-dependent T cells, such that maximal responsiveness was achieved at lower IL-2 doses, as compared with normal plasma. Post-DST+A plasma also enhanced the response to suboptimal IL-2 doses. However at saturating IL-2 doses, the maximum response was markedly inhibited by post-DST+A plasma as compared with normal or pre-DST+A plasma. Neither toxicity nor inhibition of the IL-2 response was observed when the IL-2-dependent indicator cells were preincubated in post-DST+A plasma prior to an IL-2 dose-response assay. Of the recipients whose plasma was examined, nearly all exhibited some degree of inhibition (range: 8-50% inhibition) of the response to saturating levels of IL-2. Only one renal allograft has been lost in these recipients due to rejection, and this was an accelerated acute rejection in a recipient who had rejected 2 previous allografts and who developed a "transient" positive crossmatch to his donor during DST+A. The results suggest that inhibition of IL-2 responsiveness may be a frequent consequence of DST+A, and that the inhibition is dependent on an IL-2-mediated effect distinct from proliferation. Thus, such inhibition may contribute to the salutary effect of DST+A on renal transplantation.

Azathioprine↗

Benign extrinsic compression of the common bile duct: a case report.

Painless obstructive jaundice is usually the result of malignant compression of the distal common bile duct. Infrequently extrinsic benign lesions may also cause ductal obstruction and be mistaken for a malignant process. A case of compression of the distal common bile duct is described. Preoperative evaluation was most consistent with a cystadenocarcinoma of the head of the pancreas. At operation we found an enlarged and calcified periductal lymph node with associated fibrosis and compression and obstruction of the distal common duct. Massive dilatation of the distal common duct and the cystic duct remnant gave it the appearance of a cystic mass in the superior border of the head of the pancreas. Resection and choledochoduodenostomy were curative.

Aged↗

Thrombolytic therapy for acute arterial occlusion.

To evaluate the role of selective intra-arterial low-dose thrombolytic therapy (SILDT) as an alternative to the surgical management of acute arterial occlusion, the hospital records of 40 patients who underwent 43 SILDT treatments with either streptokinase (36) or urokinase (7) between December 1979 and March 1984 were reviewed. Twenty-eight patients underwent 30 treatments (group 1) for native arterial occlusion and 12 patients underwent 13 treatments (group 2) for prosthetic or autogenous graft occlusions. Therapy was deemed successful if subsequent surgical therapy was obviated. In group 1, SILDT was successful in 13 of 28 (45%) patients with 12 of 25 lower extremity occlusions and one of three upper extremity occlusions. Successful lysis in the native artery occlusion group fell into three categories: five patients were successfully treated for arterial thrombosis complicating percutaneous transluminal angioplasty (PTA); four patients required PTA after complete lysis revealed an underlying arterial stenosis; and only three required no further therapy after SILDT. SILDT failed in all three patients with the aortoiliac occlusions. Eleven patients with femoral artery occlusions and unsuccessful SILDT required six bypass procedures, three amputations, one embolectomy, and one PTA. In group 2 only 3 of 14 treatments (21%) were successful. Bypass revision was not possible in 11 patients and all required amputation. Systemic fibrinolysis was seen in 20 (59%) of 34 patients with available data. Neither fibrinogen levels nor fibrin degradation products predicted the occurrence of complications. Minor complications occurred in 18 of 43 (43%) treatments; small hematomas at the catheter entry site were most common. Minor complications occurred in 20 of 43 treatments (44%) and included severe local hemorrhage (four), distant bleeding (three), pulmonary embolism (four), myocardial infarction (three), unmasking of an aortoduodenal fistula (one), and clot migration requiring emergency thrombectomy (four). SILDT is most effective in acute arterial thrombosis complicating arteriography or percutaneous angioplasty. It may play a role in the patient in whom thrombolysis can reveal an underlying stenosis amenable to percutaneous angioplasty. This experience shows SILDT to be of limited value in the management of prosthetic autogenous graft occlusions. Finally, thrombolytic therapy is associated with significant morbidity and mortality rates and requires cautious monitoring to detect arterial thrombus migration, worsening tissue ischemia, venous thromboembolism, intracerebral hemorrhage, and local or systemic bleeding.

Acute Disease↗

Concomitant and secondary bacterial infection of the pus in hepatic amoebiasis.

In a series of 48 consecutive patients with clinically diagnosed uncomplicated amoebic liver abscess (ALA), the pus obtained by closed drainage of the abscess was bacteriologically sterile. Secondary bacterial infection of the ALA as a direct result of the aspiration procedure occurred in only 1 patient, the causative organism being Escherichia coli. Entamoeba histolytica was identified in a total of 39 cases (81%) by means of direct microscopy of the pus as well as culture methods.

Amebiasis↗

Renal thromboxane synthesis in excised kidney distal to renovascular lesions.

Excision of a kidney with three distinct zones of perfusion was required in a patient with renovascular hypertension. One third of the kidney was normal, one third was ischemic from a stenotic artery, and one third was severely ischemic from a completely occluded artery. This provided a unique opportunity to study renal prostaglandin production in hypoperfused and control tissue by radioimmunoassays of incubated tissue slices. The thromboxane-prostacyclin synthesis ratio for the outer cortex increased from 2.2 in control tissue to 5.8 in moderately ischemic tissue and 11.3 in severely ischemic tissue; for the inner cortex, 2.1 to 6.3 and 8.8; and for the medulla, 0.4 to 1.2 and 3.0, respectively . Similar ratios were noted for thromboxane-prostaglandin E2. This correlates, for the first time in man, absolute and relative increases in renal thromboxane synthesis with renovascular hypertension.

Humans↗