Identification of uric acid and xanthine oxidase in atherosclerotic plaque.

Concentrations of uric acid in carotid endarterectomy specimens in men and women were measured using high-performance liquid chromatography in comparison wo nonatherosclerotic control specimens.

Atrial natriuretic peptide replacement therapy in rats subjected to biatrial appendectomy.

The postoperative fluid retention found in some patients after the Cox maze procedure has been attributed to surgically induced loss of atrial natriuretic peptide. We postulated that exogenous atrial natriuretic peptide could reverse this antidiuresis. A rat model was used to investigate this hypothesis. In group I, the sham group, the atrial appendages were left intact and the animals were then subjected to a fluid challenge equivalent to 1% of the animal's body weight. In group II, after biatrial appendectomy, the animals were subjected to a fluid challenge similar to that in group I. Animals in group III underwent the same protocol as that for group II plus intravenous administration of atriopeptin III at varying concentrations. Urine output and plasma atrial natriuretic peptide levels were significantly decreased after biatrial appendectomies (p < or = 0.01). Urine output returned to control levels after biatrial appendectomies with low-dose atrial natriuretic peptide infusion (0.5 pmol/min = 25.5 pg/min), although circulating atrial natriuretic peptide levels were lower. Urine output and plasma atrial natriuretic peptide levels increased with atrial natriuretic peptide infusions between 0.5 and 50 pmol/min. Heart rate and mean blood pressure did not vary significantly with atrial natriuretic peptide infusions. Thus atrial natriuretic peptide can be used effectively in low doses to induce a diuresis after biatrial appendectomies. Atrial natriuretic peptide may have clinical application after the Cox maze procedure.

Arachidonic acid metabolism and cerebral blood flow in the normal, ischemic, and reperfused gerbil brain. Inhibition of ischemia-reperfusion-induced cerebral injury by a platelet-activating factor antagonist (BN 52021).

Cerebral ischemia and ischemia-reperfusion induced cerebral injury results in the accumulation of free fatty acids and diacylglycerols as a result of increased activity of phospholipases A and C. We have evaluated the incorporation of 14C arachidonic acid into the whole brain and synaptoneurosomes, the effect of cerebral ischemia on 14C incorporation, and the effect of a PAF antagonist (BN 52021) on cerebral blood flow, free fatty acids, diacylglycerols, and polyphosphoinositides. Peak incorporation of 14C arachidonic acid into the whole brain and synaptoneurosomal fractions occurred 30 minutes following intraventricular injection. Peak incorporation into cerebellar synaptoneurosomal fractions was at 60 minutes following intraventricular injection. Turnover in phospholipid pools was similar in the whole brain and synaptoneurosomes (PI greater than PC greater than PE). Considering phosphatidylinositol content in the gerbil brain, the specific activity of 14C arachidonic acid was 22 times greater in PI than PC. Five minutes of bilateral carotid artery ligation resulted in decreased phosphatidylinositol and polyphosphoinositols. Bilateral carotid artery ligation resulted in systemic arterial hypertension, complete forebrain ischemia (CBF less than 7 ml/100 gm/min) and a 20% to 50% reduction in midbrain CBF. Reperfusion resulted in cerebral reactive hyperemia and systemic hypotension. BN 52021 inhibited the maturation of ischemia-reperfusion induced cerebral injury. Cerebral blood flow was improved. Free fatty acids were decreased, suggesting inhibition of phospholipase A activity. Decreased DAG pools with increased PIP2 pools suggest a possible coinhibition of phospholipase C.

Investigations of factors influencing the prognosis of colon cancer.

Six hundred sixty patients from Downstate and Hackensack Medical Centers were restaged and reviewed to establish correlations with survival using Cox's proportional hazards model. Age, sex, tumor size, and total nodes examined in patients with involved nodes did not correlate with survival. Tumor depth, number of involved nodes, and total nodes examined in patients with uninvolved nodes did correlate with survival. Patients with metastatic invasion into an adjacent organ with uninvolved nodes had an excellent 5 year survival rate compared with patients who had full-thickness invasion into the serosa with uninvolved nodes. These observations need to be confirmed. The relationship of some of these factors to currently used staging systems has also been discussed.

Is percutaneous balloon angioplasty appropriate in the treatment of graft and anastomotic lesions responsible for failing vein bypasses?

We reviewed 95 cases of vein graft and anastomotic lesions treated with percutaneous transluminal balloon angioplasty (PTA) and 30 cases treated surgically. The therapy was deemed a failure if the lesion recurred or if the graft closed. The 21-month patency rate of lesions treated surgically was 86%, which was significantly better than the 42% patency rate for all lesions treated with PTA (P < 0.01). An evaluation of the lesion and graft characteristics that could influence the patency of stenotic lesions treated with PTA included: lesion length, minimum graft diameter, lesion location, and lesion type. The 66% patency rate at 24 months for the 41 simple lesions (single, nonrecurrent, < 15 mm in length, and within grafts > or = 3 mm minimal diameter) was significantly better than the 17% patency rate for the 50 complex lesions (multiple, recurrent, > or = 15 mm in length, or within grafts < 3 mm in minimal diameter) (P < 0.01). In addition, the 21-month patency rate for the surgically treated group (86%) was not significantly better than that of the angioplasty-treated simple lesions (66%). When feasible, vein graft lesions are best treated with simple surgical interventions. PTA can be useful to maintain the patency of severely compromised grafts prior to surgical repair, to treat simple lesions difficult to reach surgically, and for patients with medical contraindications for an operation.

A new look at intraoperative completion arteriography: classification and management strategies for intraluminal defects.

Completion arteriography is widely regarded as an essential component of infrainguinal bypasses. However, the significance of various intraluminal filling defects is poorly defined, and strategies for managing these defects are unclear. Completion arteriography was performed by a standard technique in 78 infrapopliteal bypasses and were evaluated prospectively for the presence of angiographic defects. Thirty-nine arteriograms (50%) had no visible abnormality (grade O). Six arteriograms (8%) had minimal (grade I) defects, i.e., round lucencies (bubbles) or valve leaflets. Eighteen arteriograms (23%) had moderate (grade II) defects, i.e., uniform smooth tapering (up to 90% of luminal diameter) of the graft or outflow artery, irregular intraluminal filling defect (less than 60% of luminal diameter) within the distal graft or its adjacent outflow artery, or incomplete or faint graft opacification. Fifteen arteriograms (19%) had severe (grade III) defects, i.e., total cutoff of graft or outflow artery opacification or irregular intraluminal filling defect (greater than 60%) in the distal graft or adjacent outflow artery. Completion arteriograms were further stratified for type of bypass and outflow characteristics. All 24 bypasses with grade I or grade II defects on completion arteriography had no further surgical treatment. However, the 18 bypasses with grade II defects on completion arteriography had minimal nonsurgical manipulations consisting of repeat arteriography without or with papaverine infusion or urokinase instillation. In all 18, repeat arteriography showed improvement in the defect. The 15 bypasses with grade III defects had further surgical intervention (graftotomy, thrombectomy, vein patching, interposition graft, or graft extension). One-month and 1-year patency rates for grafts with grade I and grade II defects (87% and 79%, respectively) were not significantly worse than those for the 39 grafts with no arteriographic abnormalities (87% and 82%, respectively). In contrast, grafts with grade III defects had significantly worse (p < 0.01) 1-month and 1-year patency rates (33% and 20%, respectively) despite aggressive surgical correction of the arteriographic defects. These results emphasize the value of repeat completion arteriography and minimal interventional strategies when grade I or II defects are seen on arteriography. The poor outcome with surgical correction of grade III defects suggests that completion arteriography may not always define the full extent of the problem or that the corrective surgical maneuvers were either incomplete or detrimental.

Transfemoral endovascular stented graft treatment of aorto-iliac and femoropopliteal occlusive disease for limb salvage.

BACKGROUND: Endovascular stented grafts employ a new technique that blends intravascular stent and prosthetic graft technologies. These devices may be used to treat arterial aneurysms, occlusive disease, and vascular injuries. This report describes the application of stented grafts to the treatment of limb-threatening ischemia secondary to occlusive disease of the aorta, iliac, and femoral arteries. METHODS: Three patients with limb-threatening ischemia and severe comorbid medical illnesses were treated with transvascular stented grafts that were composed of 6-mm thin-walled polytetrafluoroethylene grafts and Palmaz balloon expandable stents. The grafts were inserted through a cutdown in an artery remote from the site of occlusion and introduced into the vascular system within 14-Fr introducer sheaths. RESULTS: Technical success was documented in all three patients with restoration of arterial continuity following stent graft deployment. Patency and limb salvage has been achieved to 1 year. One patient required further dilatation of the proximal stent at 6 weeks. Complications were limited to an iliofemoral deep vein thrombosis in one patient. CONCLUSIONS: Endovascular stented grafts can be inserted to treat limb-threatening ischemia. Although these initial results are encouraging, greater experience in more patients observed for longer periods of time is necessary before this technique can be advocated for widespread use.

Endoluminal treatment of vascular occlusive disease.

The logical desire to avoid major cutaneous incisions and surgical dissection in the treatment of vascular occlusive disease has, in recent years, led to a surge of new therapeutic options whereby access to the diseased blood vessel is obtained via a distant site and treatment is effected from within the vessel. Such endoluminal treatment modalities include thrombolysis, balloon angioplasty, atherectomy, stenting, and stent grafting. For the purpose of this surgically oriented article, the latter two techniques are discussed.

Arterial embolectomy: a 34-year experience with 400 cases.

A series of 400 peripheral arterial embolectomies performed in 326 patients over a 34-year period is presented. Operative mortality was 11.0 per cent overall and 10.0 per cent in patients after the introduction and use of Fogarty catheters. The plateau in mortality is related to the association with serious underlying cardiac disease. The amputation rate was 9.5 per cent, with a corresponding 90.5 per cent limb salvage rate. Cardiac disease was the most common cause of emboli and was responsible for the majority of deaths. Mortality was considerably higher in patients with aortic and iliac emboli and in patients with recent myocardial infarcts. Amputation rates were higher with femoral and popliteal emboli and correlated directly with the time delay from onset of symptoms to performance of embolectomy. Higher amputation rates in the second half of the series are related to liberalization of the indications for embolectomy. Prompt operative management of patients with peripheral arterial emboli remains the treatment of choice. Low mortality and amputation rates can be achieved with early embolectomy and routine use of heparin.

Platelet-activating factor and polyunsaturated fatty acids in cerebral ischemia or convulsions: intracellular PAF-binding sites and activation of a fos/jun/AP-1 transcriptional signaling system.

Platelet-activating factor (PAF) is a lipid mediator formed in the early response of the central nervous system to ischemia or convulsions. Free polyunsaturated fatty acids and arachidonic and docosahexaenoic acids are accumulated along with PAF. Antagonists of PAF have been found to improve cerebral blood flow and partially block the rise in free fatty acids, an effect that may arise by way of inhibition of PAF receptors or stimulation of the reacylation of free fatty acids released upon insult. Three intracellular PAF-binding sites have been identified in rat cerebral cortex. These very high-affinity binding sites are inhibited by PAF antagonists, with certain antagonists exhibiting specificity for a particular binding site. This specificity indicates heterogeneity in these binding sites. Ischemia or stimulation also leads to protooncogene transcriptional activation. Here, we discuss studies with cells in culture showing that PAF promotes transcriptional activation of immediate-early genes. PAF activates the transcription of the immediate-early genes fos and jun, whose gene products are regulators of the transcription of other genes. Transcription of fos is also activated by convulsion or ischemia in the central nervous system. The activation of these genes by PAF can be inhibited by PAF antagonists, and is apparently accomplished by way of an AP-1 transcription regulatory sequence in the promoter region of the target genes. Studies with deletion mutants show that PAF can also exert its activating properties by way of cyclic adenosine-3',5'-monophosphate-(cAMP) and Ca(2+)-responsive elements, and suggest that PAF is involved in an interconnected network of cell signaling that may coordinate short-term and long-term responses of cells to stimulus and injury.

Limb salvage surgery in end stage renal disease: is it worthwhile?

The role of limb salvage surgery in patients with end stage renal disease (ESRD) is controversial. In view of this debate, we reviewed our experience with 54 primary and 15 secondary revascularizations for limb salvage in patients with ESRD over the past decade. Thirty-seven patients required dialysis and 10 had functioning renal transplants. Severe limb threatening ischemia was the indication for all revascularizations. The 2-year cumulative secondary graft patency rate was 56.2% with an associated limb salvage rate of 71.4%. There was no significant difference in graft patency or limb salvage rates between patients requiring dialysis and those with functioning renal allografts (p = 0.5). The 30-day operative mortality for the 99 surgical procedures (69 arterial bypasses and 30 additional operations) was 13% and the 2-year patient survival was 45.6%. Six of the 15 amputations were performed despite a patent graft on limbs which had extensive infection and gangrene. We conclude that limb salvage surgery should only be undertaken with recognition of these risks in patients with ESRD or functioning renal transplants. Surgery should be performed before gangrene and infection become extensive. Patients with unrelenting infection or mid-forefoot gangrene should be considered for primary amputation.

Impaired venous hemodynamics in a minority of patients with chronic leg ulcers due to sickle cell anemia.

BACKGROUND: Chronic or recurrent leg ulceration occurs in 25% of sickle cell anemia patients, but not in the remaining 75%. Doppler studies of venous function were normal in 16 sickle cell anemia patients with leg ulcers. PATIENTS AND METHODS: Venous Duplex Ultrasound was used to study 33 sickle cell anemia patients with chronic leg ulcers. RESULTS: Six of the 33 patients had venous reflux in at least one leg. CONCLUSIONS: Venous insufficiency may contribute to the development of leg ulcers in a minority of sickle cell anemia patients. A minority of sickle cell anemia patients with chronic leg ulcers can be shown to have leg venous reflux by duplex ultrasound imaging.

High precision isotope measurements reveal poor control of copper metabolism in parkinsonism.

Disordered copper metabolism may be important in the aetiology of Parkinsonism, as caeruloplasmin is a key enzyme in handling oxidative stress and is involved in the synthesis pathway of dopamine. The human Cu metabolism of ten Parkinsonism patients was compared to ten healthy controls with the aid of a stable (65)Cu isotope tracer. The analyses of blood serum (65)Cu/(63)Cu ratios yielded individual isotopic profiles, which indicate that the Cu metabolism is less controlled in patients with Parkinsonism. Modelling based on both isotope tracer and total Cu concentrations suggests that 30% of the subjects affected by Parkinsonism have abnormally large Cu stores in tissues. To detect the small differences in Cu metabolism between Parkinsonism and controls, the analysis of stable isotope composition must be performed using multiple-collector inductively coupled plasma mass spectrometry and the associated sample preparation techniques. This pilot investigation supports full-scale medical studies into the Cu metabolism of those with Parkinsonism.

Tinnitus originating from an abnormal jugular bulb: treatment by jugular vein ligation.

Tinnitus and hearing loss can occur in patients with a high-riding abnormal jugular bulb. Jugular vein ligation in selected patients can cure tinnitus and reverse hearing loss. A 39-year-old woman reported a 4-year history of right-sided tinnitus of increasing intensity associated with a mild hearing loss. Extensive evaluation revealed only an enlarged right jugular bulb with dehiscence of the normal petrous bony septum between the bulb and the middle ear. The patient underwent ligation of the right internal jugular vein and noted immediate cessation of tinnitus and the return of normal hearing. Review of the literature suggests that jugular vein ligation is appropriate in selected cases of venous tinnitus.

Nonreversed translocated saphenous vein bypass for arterial trauma.

Nonreversed translocated saphenous vein (NTSV) bypasses were performed for 17 acute arterial injuries. The technique involved controlling hemorrhage, inserting indwelling shunts, perfusing the harvested saphenous vein with papaverine solution, placing the vein in a nonreversed orientation over the shunt, performing valvulotomy under arterial pressure with a modified Mills' valvulotome and completing the distal anastomosis just before removing the shunt. Followup ranged from 2 to 36 months. There were no graft occlusions. The advantages of using NTSV graft for reconstruction of arterial injuries include autogenous reconstruction, reduced size discrepancy between graft and artery at both the proximal and distal anastomosis, improved hemodynamics when spasm compromises distal runoff, and increased vein utilization. NTSV provides increased versatility with both large and small vessel trauma and may improve patency rates.