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Biomedical subjects

P Flanigan

Publications and source records attributed to P Flanigan.

11 recordsLinked to original sources

Circumvention of pleiotropic drug resistance in subcutaneous tumours in vivo with verapamil and clomipramine.

The development of pleiotropic drug resistance (PDR) in vivo in solid tumour models suggests that a similar process may occur in the clinic. A subline of the Ridgway osteogenic sarcoma (ROS)--a murine subcutaneously-growing solid tumour--with moderate resistance (1.5 fold) to actinomycin D was selected by repeated suboptimal treatment with this drug in vivo. This subline (ROS/ADX/G2) showed cross-resistance to vincristine (3.5 fold) and etoposide (over 5.1 fold) but not to doxorubicin. The resistance could in all cases be partly or completely overcome by treatment with non-cytotoxic doses of verapamil or clomipramine. Resistance to actinomycin in this model was associated with lower (up to 3.2 fold) drug accumulation into tumours which could be increased (up to 2.8 fold) by treatment with 25 micrograms/g verapamil. These data support clinical trials of the use of membrane-active agents to overcome PDR.

Animals↗

Autogenous vein graft repair of injured extremity arteries: early and late results with 134 consecutive patients.

Autogenous vein tissue is recognized as the preferred material for extremity revascularizations that require the use of a conduit. However, the results after vascular repair of injured extremity arteries with autogenous vein interposition or bypass grafts have not been well defined. This study was done to determine both the early and late patency and limb salvage rates as well as the graft infection rate of autogenous vein repairs of injured extremity arteries. The records of 134 consecutive patients with acute extremity arterial injuries requiring repair with a reversed autogenous vein graft over a recent 5-year period were reviewed. Follow-up graft patency was defined by the presence of a palpable pulse and an extremity Doppler-derived pressure index of greater than or equal to 0.9 distal to the arterial repair. Cumulative patency was assessed by the life-table method. Acute graft thrombosis occurred in two patients, one of whom underwent successful graft thrombectomy. Four patients (3%) required extremity amputation: one patient with a thrombosed vein graft and three patients with patent vein grafts but nonsalvageable limbs as a result of myonecrosis (2) or osteomyelitis (1). No perioperative graft infections occurred. One hundred twenty-eight patients (97%) had an intact extremity and a patent vein graft at the time of hospital discharge. One hundred three patients (80%) were examined at 30 days, and all grafts were patent. Seventy-three patients (57%) were available for follow-up at intervals exceeding 6 months, and 40 patients (31%) were followed-up for periods exceeding 24 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Microvascular disease and limited joint mobility in diabetes. A comparison of fibrinolysis and prostacyclin in diabetes and systemic sclerosis.

The pathogenesis of Limited Joint Mobility (LJM) in diabetes is unknown, but the abnormality is said to be associated with an increased incidence of microangiopathy. To examine the possibility that LJM may be a manifestation of microvascular disease, fibrinolysis and blood prostacyclin metabolites were measured in diabetic patients with and without LJM, and compared with patients who have systemic sclerosis (PSS). The concentrations of plasma fibrinogen (p less than 0.01) and Plasminogen Activator Activity (PAA) (p less than 0.02) were increased in both diabetic groups, compared with non-diabetic controls, and were of similar magnitude to the changes observed in PSS. Antithrombin III (AT III) activity was significantly lower in diabetic patients with LJM than in those without LJM, but not significantly different from controls. Prostacyclin concentrations were raised in PSS patients compared to controls (p less than 0.02) but were not raised in diabetic subjects. Thus abnormal fibrinolysis was demonstrated in diabetic patients compared to non-diabetic controls, and prostacyclin concentrations in diabetics were lower than in PSS patients. The diabetic patients with LJM had lower AT III activity than diabetics without LJM, but overall a convincing difference between the two groups of diabetics was not proven. No sure inferences could be drawn on the vascular aetiology of LJM, while the impaired prostacyclin activity might contribute to the development of diabetic microangiopathy.

Adult↗

Crush syndrome due to limb compression.

Four patients with the crush syndrome due to prolonged limb compression were treated at Cook County Hospital, Chicago. Limb injury was caused when the obtunded patient fell asleep lying on the involved extremity. Prolonged limb compression may cause an acute compartment syndrome with ischemic muscle injury. Continued muscle ischemia may lead to myonecrosis resulting in shock or renal failure. A history of prolonged limb compression with a swollen limb should suggest the diagnosis of crush syndrome. Prompt therapy, including rapid correction of volume and metabolic derangements, extensive open fasciotomy, and dialysis for severe acute renal failure should provide good functional results in the majority of patients.

Acute Kidney Injury↗

Peripheral vascular trauma from close-range shotgun injuries.

This report summarizes an eight-year experience (1976 to 1983) with 49 close-range shotgun blasts with associated major vascular injuries seen in a large urban hospital. Injuries to the upper extremity (40%), lower extremity (56%), and neck (4%) were seen. A high frequency of associated deep venous injury (82%), nerve injury (37%), fracture (33%), massive soft-tissue loss (43%), and compartmental hypertension (39%) was observed. There were no deaths in this series, and the limb salvage rate was 96%. Neither patient with multiple carotid artery injuries suffered a neurologic deficit. We attribute our success in the management of these complex injuries to rapid fracture immobilization, early and aggressive use of fasciotomy, adequate débridement of devitalized tissue, repair of deep venous injuries, arterial repair with autogenous tissue, and extra-anatomic bypass grafting in selected cases.

Adolescent↗

Cardiovascular lymphoscintigraphy.

The technique of lymphoscintigraphy when applied to the heart and blood vessels correlates well with results of anatomic investigations of arterial and cardiac lymphatic vessels reported in the literature. Five dogs and eight rabbits underwent lymphoscintigraphy of the heart and aorta, as well as the iliac, femoral, and tibial arteries. After surgical exposure, approximately 500 microCi of 99mTc-labelled antimony sulfide was injected into the myocardium or the adventitial-medial plane of an artery. The colloid particle size of 4 to 12 m mu causes resorption and transport only via the lymphatic vessels. Twenty-one preparations were imaged from 2 to 48 hours after administration. This method provides a functional demonstration that the tibial and femoral arteries of both species are invested with lymphatics. The first echelon of lymph nodes which drain muscular arteries are imaged within 2 hours. Regional lymph nodes could not be seen to drain the aorta or iliac arteries. Anterior left ventricular myocardial injection in the dog showed a single cardiac lymph node. This drainage pattern has been described previously by other investigators. In the rabbit a similarly placed injection visualized a group of regional cardiac nodes. Ligation of the collecting ducts afferent to the cardiac node in the dog prevented removal of the isotope from the heart at 3, 6, and 9 hours. At 24 hours the liver and spleen were imaged, the radiocolloid gaining entrance to the blood vascular system presumably via myocardial lymphaticovenous anastomoses. Lymphoscintigraphy reflects physiologic processes such as lymph transport, filtration, and reticuloendothelial function. It defines regional patterns of cardiac and arterial lymph drainage. It can confirm experimentally produced impairment of lymph drainage from a defined area of tissue. Lymphoscintigraphy should be useful in the investigation of the significance of lymph drainage to diseases of the heart and blood vessels.

Animals↗

Neonatal abdominal aortic thrombosis.

Thromboembolism of abdominal aorta and its branches after umbilical artery catheterization has been previously reported. In the past, total occlusion of the abdominal aorta and its major branches was associated with high mortality. Successful aortic thrombectomy in the neonatal period has been reported only once in English literature. The successful management of 2 infants described here shows the need for early diagnosis and aggressive approach, including surgical thrombectomy when indicated. Thromboembolism of abdominal aorta and iliac arteries can be diagnosed by noninvasive methods, such as 2-dimensional echoaortography and Doppler blood flow measurement.

Aorta, Abdominal↗

Chronic upper extremity arterial insufficiency. Etiology, manifestations, and operative management.

Forty-eight arterial reconstructions were performed for chronic upper extremity ischemia in 43 patients, aged 31 to 81 years. Diagnostic arterial catheterization was the most frequent cause of symptomatic occlusion, followed by proximal arteriosclerotic lesions and noniatrogenic trauma. Doppler ultrasound evaluation provided important diagnostic and prognostic data that complemented information derived from arteriography. Indications for operation included disabling claudication (39 cases) or digital gangrene (four cases). Restoration of normal extremity function can be anticipated except in instances where poor forearm runoff exists. Autogenous saphenous and basilic interposition vein grafts have proved excellent for axillary-brachial revascularizations. Axillary-axillary bypass procedures for innominate-subclavian artery occlusions appear hemodynamically sound and technically simple. Follow-up, averaging 48 months, extended to 144 months. Late vein graft failure or progressive distal occlusive disease was not encountered.

Adult↗

Rational approach to the differentiation of vascular and neurogenic claudication.

Lower extremity pain caused by exercise but relieved by rest is usually a reliable symptom of chronic arterial insufficiency. However, similar discomfort often occurs in patients with neurospinal compression. Furthermore, arterial occlusive disease and demonstrable spinal stenosis may be present simultaneously. Fifty-two patients with symptoms suggesting intermittent claudication comprised the study group. All were proven to have a nonarterial cause of their complaint. The study consists of a retrospective analysis of the diagnostic methods used in confirming the proper diagnosis. Conclusions reached suggest a rational approach to solution of individual patient problems. The nonvascular origin of the symptoms was suggested initially by clinical evaluation in 19 patients, and by noninvasive arterial evaluation in an additional 22. The neurospinal origin of symptoms was obscured in 11 patients because of the presence of significant arterial occlusive disease, as demonstrated by nominvasive arterial testing. Seven of the 11 patients underwent arterial reconstruction, which failed to relieve their symptoms. Subsequently, the neurospinal origin of these symptoms was proven by appropriate treatment. This experience has shown that the errors in diagnosis and treatment could have been avoided by using a combined diagnostic approach, correlating results of an accurate clinical evaluation with noninvasive arterial testing as well as the findings shown on lumbosacral spine films.

Adult↗

Indirect assessment of carotid occlusive disease by ocular pneumoplethysmography. 500 mm Hg vacuum pressure measurements and ocular pulse timing.

The interpretation and diagnostic value of the ophthalmic artery pressure measurement and ocular pulse timing modes of the 500 mm Hg vacuum OPG-Gee ocular pneumoplethysmograph were evaluated in 65 patients who underwent aortic arch and cerebral arteriography. Data analysis revealed the OPG-Gee differential tracing which electronically compares and amplifies differences between the right and left eye pulse waveforms to be of little value. In predicting the presence of a greater than or equal to 50 percent diameter unilateral stenosis, an eye-eye pulse interval of greater than 15 msec was 82 percent accurate, a greater than or equal to 5 mm Hg ophthalmic artery pressure difference was 77 percent accurate and when combined these two criteria were 84 percent accurate. Neither of the criteria intended to detect bilateral carotid lesions, eye-ear pulse interval nor ophthalmic/brachial pressure index, were reliable. Ocular pulse timing was found to be highly specific but insensitive to hemodynamically significant carotid disease. OPG-Gee pressure determinations were more sensitive but lacked specificity. In combination, these criteria allowed identification of unilateral hemodynamically significant lesions with a sensitivity of 83 percent and a specificity of 86 percent. If used to detect more severe degrees of arteriographic stenosis, 60 and 70 percent diameter reduction, the overall diagnostic accuracy of these techniques was not improved. These results do not justify the use of the OPG-Gee instrument as a single noninvasive test for carotid arterial disease.

Arterial Occlusive Diseases↗