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Biomedical subjects

M B Freeman

Publications and source records attributed to M B Freeman.

43 records · Page 3Linked to original sources
PubMed1988

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↗
PubMed1987

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↗
PubMed1981

Role of intravenous hyperalimentation as an adjunct to intensive chemotherapy for small cell bronchogenic carcinoma.

Forty-nine patients with small cell bronchogenic carcinoma (23 limited and 26 extensive disease) received their first two of three courses of intensive remission induction chemotherapy with (21 patients) or without (28 patients) intravenous hyperalimentation (IVH). The chemotherapy included six remission induction courses with ECHO (epipodophyllotoxin VP-16-213, cyclophosphamide, hydroxydaunorubicin, oncovin), followed by six courses of maintenance with PRIME (procarbazine, ifosfamide, methotrexate). Prophylactic brain irradiation (3000 r/2 weeks) was given to all patients and those with limited disease received chest irradiation (5000 r/5 weeks) at the completion of ECHO. Thus far, all 30 patients who have completed three courses of ECHO have responded with complete (70% CR) or partial (30% PR) remissions. The CR rate was higher for patients receiving IVH (85% vs 59%, P = 0.25). Myelosuppression was pronounced and predominantly in the form of neutropenia. Median lowest neutrophil counts were zero during each of the three courses of ECHO and lasted a median of 5 days at levels less than 500/mm3. Major infections occurred in 21% of courses. The administration of IVH did not ameliorate the hematologic, gastrointestinal, and infectious morbidity of ECHO chemotherapy. However, it resulted in preservation of body weight (P less than 0.01) and improved skin reactivity to a battery of six skin antigens (P = 0.03). The administration of intensive therapy with ECHO +/- IVH was well tolerated and resulted in high CR rates in patients with small cell bronchogenic carcinoma. The administration of IVH was most helpful in preventing severe weight loss and augmenting response to a battery of skin antigens. The long term survival effects of these observations are yet to be determined.

Adult↗
PubMedDate not supplied

Viatical settlements: what case managers should know.

Culturally we are taught not to discuss money and other people's financial circumstances, particularly if financial hardship exists. The reluctance is even greater if that hardship involves dire circumstances like a serious illness. Added to this reticence is anecdotal evidence that case managers (and other professionals who may be called to interact with clients regarding a broad range of stressful issues during ill health) are hesitant to discuss financial matters other than those directly pertaining to payment for specific, predetermined medical treatment.

Case Management↗
PubMedDate not supplied

The use of radionuclide angiography to study blood flow through endothelial cell seeded extrathoracic bypass grafts in the dog.

Endothelial seeding of vascular grafts has been shown to decrease graft thrombogenicity and prolong longevity when implanted in vivo. Previous studies have utilized anatomic grafts to study endothelialization and healing. Anatomic thoracoabdominal grafts do not allow for sequential biopsy for evaluation of individual grafts nor do they approximate the environment for long bypass grafts used in limb salvage. This study evaluated the use of an extra-anatomic aortic bypass graft to assess the healing of endothelial cell seeded expanded polytetrafluoroethylene (ePTFE). Radionuclide angiography was used to evaluate graft patency and quantify blood flow through the graft. Dogs underwent placement of an extra-anatomic 60 cm long, 8 mm internal diameter, graft seeded with autologous endothelium. Grafts were biopsied from 2 weeks up to 1 year. Radionuclide studies were performed postimplantation and following each graft biopsy. Graft placement and biopsies were well tolerated in all dogs. Biopsied segments of graft allowed for sequential studies of the healing of implanted grafts by scanning electron and light microscopy. Flow through the implanted graft was close to 50% of the total caudal abdominal aortic flow. No significant difference in graft flow was noted either between animals or over time.

Anastomosis, Surgical↗
PubMedDate not supplied

Synthetic vascular grafts seeded with genetically modified endothelium in the dog: evaluation of the effect of seeding technique and retroviral vector on cell persistence in vivo.

Unique characteristics of endothelium make it an attractive target cell for gene transfer. Genetically modified endothelial cells (ECs) seeded on synthetic vascular grafts offer the potential to control neointimal hyperplasia, decrease graft thrombogenicity and improve small diameter graft patency. This study addresses the issue of synthetic vascular graft colonization with endothelial cells transduced with noninducible retroviral marker genes in the dog. Autologous endothelial cells were enzymatically harvested and transduced with either the bacterial NeoR gene or human growth hormone gene using retroviral vectors. All transduced cells were positive by polymerase chain reaction (PCR) amplification for the transduced gene sequence prior to graft seeding. Transduced ECs were seeded on Dacron grafts (n = 3) preclotted with autologous blood. These grafts exhibited complete endothelialization at times from 250 to 360 days. Recovered DNA, however, was negative for the transduced gene sequence when analyzed by PCR and Southern blotting. Expanded polytetrafluoroethylene (ePTFE) was evaluated (n = 8) using several different cell seeding protocols. Grafts were seeded at 3 densities (ranging from 6 x 10(3) to 1.5 x 10(5) cells/cm2) and 2 different adherence times. Seeding substrate was also evaluated. Grafts were either preclotted with whole blood or incubated with 20 or 120 micrograms/ml fibronectin for 60 min. Graft biopsies were evaluated from 2 to 52 wk. Limited endothelialization was present in 4 dogs as early as 2 wk, but never progressed to full luminal coverage. The remaining dogs failed to ever exhibit any luminal EC adherence. Two dogs with limited EC coverage had positive DNA by PCR for the NeoR gene sequence at 2 and 3 wk. In contrast to transduced EC's, nontransduced EC colonization of ePTFE was complete at 2 wk when seeded under conditions that transduced cells had failed to persist. Neither seeding density, adherence time, seeding substrate or retroviral vector used influenced the uniformly poor graft coverage seen with transduced cells. Results of this study indicate that despite successful gene transfer using 4 different retroviral vectors, transduced endothelial cells seeded under varying conditions appear altered in their ability to stably adhere and colonize synthetic vascular grafts in vivo.

Animals↗