Biomedical subjects

Donald Silver

Publications and source records attributed to Donald Silver.

9 recordsLinked to original sources

PubMed2004

Inhibition of intimal hyperplasia by direct thrombin inhibitors in an animal vein bypass model.

Many functions of the coagulation system have nonthrombotic effects. The indirect thrombin inhibitor heparin has been previously shown to be effective in limiting intimal hyperplasia (IH). We sought to study the effect of thrombin on IH by using two direct thrombin inhibitors (DTIs), argatroban and lepirudin. Sprague-Dawley rats underwent interposition vein grafting to the carotid artery. Vein grafts were treated with either saline (n = 6) or one of the two DTIs (n = 6 for both). At 30 days, the rats were sacrificed and vessels were perfusion fixed. Sections of the proximal carotid artery, graft, and both anastomoses were stained with both hematoxlyin/eosin and von Gieson's elastin stain. Sections were examined and compared for luminal area and intima-to-media (IM) ratio. The vessels treated with DTIs had less (p < 0.05) IH (IM ratio for proximal anastomosis: control 1.036 +/- 0.857, lepirudin 0.373 +/- 0.21, argatroban 0.182 +/- 0.118) and better lumen preservation than the control vessels (lumen area of proximal anastomosis: control 1.69 +/- 0.9, lepirudin 2.45 +/- 0.74, argatroban 2.81 +/- 0.78). There were no thromboses in the DTI-treated vessels. Dilatation of the graft segment was noted in the argatroban group. Thus, DTIs are effective at reducing IH in a small-animal model, suggesting that inhibition of thrombin has a protective role in IH. In addition, a difference of action between DTIs is suggested by the dilatation seen only in the argatroban-treated graft sections.

Anastomosis, Surgical↗

PubMed2004

Heparin-associated antiplatelet antibodies increase morbidity and mortality in hemodialysis patients.

BACKGROUND: Patients are frequently exposed to heparin during hemodialysis (HD) to prevent thrombosis of the extracorporeal circuit. Other groups with frequent heparin exposures have a high rate of development of heparin-associated antiplatelet antibodies (HAAb). We sought to define the prevalence of HAAb in HD patients and evaluate their effects. METHODS: A chart listing of all patients undergoing HD at our tertiary care institution during a six-year period was obtained. Charts of patients who tested positive for HAAb were reviewed. A cohort of randomly selected HD patients who tested negative for HAAb was analyzed as a control group. RESULTS: In our sample, 3.7% of HD patients were positive for HAAb. Morbidity, as defined by thromboembolic (TEC) or hemorrhagic complications, was higher in the HAAb-positive group compared with the control patients (60% vs 8.7%, P < .05), and the mortality rate (mortality directly related to TECs) was also higher in the HAAb-positive patients (28.6% vs 4.35%, P < .05). CONCLUSIONS: Contrary to reports of HAAb in patients undergoing HD without increased morbidity and mortality, we found significant increases in both morbidity and mortality. The elevated morbidity and mortality may represent ongoing endothelial and platelet activation from repeated heparin exposures. Reduced morbidity and mortality will likely require early recognition of HAAb and alteration of anticoagulation in HD patients.

Adult↗

PubMed2003

Heparin-induced thrombocytopenia: twenty-nine years later.

OBJECTIVE: To determine the current frequency, types of patients, indications for testing, morbidity and mortality, and management of heparin-induced thrombocytopenia (HIT). METHODS: Between December 1998 and July 2001, the charts of 102 inpatients that tested positive for heparin-associated antiplatelet antibodies (HAAb) were reviewed. There were 33,941 inpatients, 10,348 of them having received unfractionated or low molecular weight heparins. HAAb were determined by platelet aggregometry. RESULTS: There were 58 males and 44 females with a mean age of 56 years. The majority (72%) of patients were admitted to a surgical service (23% were admitted to medicine, and 5% were admitted to obstetrics/pediatrics). Indications for testing included one or more low platelet counts (n = 51), unexplained arterial (n = 33) or venous (n = 6) thromboses, resistance to anticoagulation (n = 1), prior history of HAAb (n = 3), organ transplant (n = 17), or other indication (n = 4). The HAAb "patterns" were variable, with patients having antibodies only to bovine (n = 7) or porcine heparin (n = 5), bovine and porcine heparins (n = 17), enoxaparin (n = 3), fragmin (n = 7), or all 4 heparins (n = 43). The HIT-related mortality was 6.9%, and the morbidity was 30% with 19 arterial and 7 venous thromboses and 5 bleeding events. Management consisted of discontinuation of heparin in 95 patients. Twenty-five patients did not require continued anticoagulation. When needed, anticoagulation was continued with a direct thrombin inhibitor (n = 32), enoxaparin (n = 16), warfarin (n = 15), or aspirin (n = 7). Seven patients continued to receive unfractionated heparin (n = 4) or low molecular weight heparin (n = 3). CONCLUSIONS: HIT occurs in 0.99% of inpatients receiving heparin and remains an important nondiscriminatory contributor to their morbidity and mortality. Patients receiving any form of heparin who develop a decreasing platelet count, unexplained thrombosis, or resistance to heparin anticoagulation should be tested for HAAb. If HAAb are detected, patients must not receive the sensitizing heparin(s).

Adolescent↗

PubMed2002

Abdominal aortic sarcoma: report of a case with long-term survival and review of the literature.

We present a case of an intimal epitheliod aortic sarcoma. Diagnosis was established after an aortic endarterectomy. The tumor was subsequently resected and an aortic graft was inserted. The patient underwent adjuvant chemotherapy. The patient is alive and free of metastatic disease at 48 months. Aortic tumors are rare, with an extremely poor prognosis and 1-year survival of 0-13%. The diagnosis is usually established postmortem, with metastatic disease being a common finding. The diagnosis should be suspected in patients with symptoms of nonatherosclerotic-related aortic occlusive disease or distal embolic events. Resection followed by adjuvant therapy and close follow-up can offer a prolonged survival for the patient with an extremely lethal aortic sarcoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Small bowel motility and transit after aortic surgery.

OBJECTIVE: The inability to tolerate feedings after aortic surgery prolongs hospitalization. The aim of this study was to define jejunal manometric and small bowel transit characteristics associated with the ileus that follows transperitoneal aortic surgery. METHODS: Five male patients who underwent transperitoneal infrarenal aortobifemoral bypass had intraoperative placement of a jejunal multilumen catheter. The open abdomen allowed precise placement of pressure recording ports at 20, 22, 24, 26, 28, and 38 cm past the ligament of Treitz. Three-hour manometric studies were done after surgery and for 3 postoperative days. The migrating motor complex was identified visually on the manometric tracings, and pressure waves were identified with computer and a motility index calculated. Motility data were compared with healthy control data previously reported in the literature. Small bowel transit was determined with barium and serial abdominal radiographs. RESULTS: All patients had ileus develop with return of bowel sounds at 2 to 7 days (median, 6 days) and flatus at 3 to 9 days (median, 7 days) after surgery. Jejunal motor activity was present within 6 hours of surgery, but the motility index was less in patients then in control subjects. The postoperative migrating motor complexes differed from control subjects in having more phase I, less phase II, and more frequent phase IIIs. Phase III retrograde migration was common in the patients but not in the control subjects. Small bowel transit was 2 days or greater in all patients. CONCLUSION: Motor activity is present in the jejunum shortly after aortic surgery. However, the activity is decreased in intensity and the fasting cycle differs from control subjects. Retrograde migration of phase III is the most likely abnormality, resulting in delayed small bowel transit. The data would predict a high rate of enteral feeding intolerance early after surgery. Future studies should focus on pharmacologic manipulation to rapidly return small bowel motility to a more normal state after aortic surgery.

Aged↗

PubMedDate not supplied

Heparin-induced thrombocytopenia: pathophysiology and management.

Immune-mediated heparin-induced thrombocytopenia (HIT) is a well-defined syndrome. Clinical criteria (thrombocytopenia, resistance to heparin anticoagulation, or thromboses during heparin therapy) are defined, and serologic diagnostic tests are available. Earlier recognition of HIT syndrome has allowed for significant advances in therapy, leading to marked reductions in morbidity and mortality from HIT syndrome. This review addresses the epidemiology, pathobiology, and management of HIT syndrome

Anticoagulants↗

PubMedDate not supplied

The Ehlers-Danlos specter revisited.

Ehlers-Danlos type IV is a major concern to vascular surgeons because it is often associated with spontaneous hemorrhage from arteries containing decreased type III collagen. Five members of a family with Ehlers-Danlos type IV and a review of another family of five with Ehlers-Danlos type IV are reported. Evaluation of the recent family included clinical evaluation as well as assay of collagen production. The age range of the three involved females and two males was 7 to 52 years. The father of the affected family had a spontaneous colon perforation at age 39. His son, at age 27, had a spontaneous rupture of the iliac artery. Revascularization was accomplished with difficulty. His daughter had a large cerebral bleed. Two granddaughters, ages 7, have not had any bleeding or aneurysmal events. The amount of type III collagen was only 10% of normal in the patient with the iliac artery rupture. The three females all exhibited similarly low levels of type III collagen. The father's type III collagen level was not sufficiently low to confirm Ehlers-Danlos type IV, although he had a spontaneous colon perforation. In the other Ehlers-Danlos type IV family of five, the three surviving members had type III collagen levels as low as 5% of normal. Two family members died after spontaneous iliac rupture at ages 24 and 33. Both families exhibited an autosomal dominant inheritance pattern. Ehlers-Danlos type IV remains a challenging problem for vascular surgeons. It is transmitted as an autosomal dominant inheritance with a high degree of penetrance. Spontaneous arterial and intestinal perforations should alert the clinician to the possibility of Ehlers-Danlos type IV. Patients should be evaluated noninvasively. Arterial repairs may not be successful in these patients because the vessels are extremely friable. Assays of collagen production are advisable in establishing the diagnosis.

Adolescent↗

PubMedDate not supplied

Gastrointestinal bleeding as the initial manifestation of a polyarteritis nodosa-associated hepatic artery aneurysm-duodenal fistula--a case report.

The authors report an unusual case of upper gastrointestinal bleeding from a hepatic artery aneurysm-duodenal fistula in a 21-year-old male. Arteriography revealed multiple visceral artery aneurysms. Biopsy of the hepatic artery aneurysm (HAA) revealed focal areas of necrosis, medial degeneration, fibrosis, and giant cells. The necrotizing vasculitis plus the multiple visceral aneurysms were highly suggestive of polyarteritis nodosa (PAN). This report reviews the pathophysiology and management of PAN and the diagnosis and management of HAA.

Adult↗

PubMedDate not supplied

Hypercoagulable states: a review.

Vascular surgeons are often asked to evaluate patients with recurrent thromboses or thromboses in unusual locations either arterial or venous. There may be obvious inciting factors, but in many of these patients the possibility of a previously undiagnosed hypercoagulable state must be considered. Hypercoagulable states can be acquired (smoking, medication, change in physiologic status as occurs with pregnancy) or congenital. Congenital hypercoagulable disorders are more prevalent in families or patients with a history of thromboembolic events early in life or multiple miscarriages and include conditions such as protein C or S deficiencies, factor V Leiden mutation, and prothrombin gene variant. This article reviews the hypercoagulable states that are encountered in clinical practice as well as guidelines for testing and goals of therapy.

Anticoagulants↗