Overexpression of petunia chalcone isomerase in tomato results in fruit containing increased levels of flavonols.

Tomatoes are an excellent source of the carotenoid lycopene, a compound that is thought to be protective against prostate cancer. They also contain small amounts of flavonoids in their peel ( approximately 5-10 mg/kg fresh weight), mainly naringenin chalcone and the flavonol rutin, a quercetin glycoside. Flavonols are very potent antioxidants, and an increasing body of epidemiological data suggests that high flavonoid intake is correlated with a decreased risk for cardiovascular disease. We have upregulated flavonol biosynthesis in the tomato in order to generate fruit with increased antioxidant capacity and a wider range of potential health benefit properties. This involved transformation of tomato with the Petunia chi-a gene encoding chalcone isomerase. Resulting transgenic tomato lines produced an increase of up to 78 fold in fruit peel flavonols, mainly due to an accumulation of rutin. No gross phenotypical differences were observed between high-flavonol transgenic and control lines. The phenotype segregated with the transgene and demonstrated a stable inheritance pattern over four subsequent generations tested thus far. Whole-fruit flavonol levels in the best of these lines are similar to those found in onions, a crop with naturally high levels of flavonol compounds. Processing of high-flavonol tomatoes demonstrated that 65% of flavonols present in the fresh fruit were retained in the processed paste, supporting their potential as raw materials for tomato-based functional food products.

Coagulation abnormalities in patients undergoing myocardial revascularization.

One hundred patients were screened for hypercoagulability preoperatively and on the third, seventh, tenth, fourteenth, and twenty-first days postoperatively. Patients found to have hypercoagulability were treated with heparin, aspirin, and Coumadin. When the abnormality was present preoperatively, treatment was continued for the duration of the patient's life. Those patients in whom abnormalities developed postoperatively were given anticoagulants until cardiac catheterization 6 months following their operation. Twenty-four of the 100 patients had no coagulation abnormalities preoperatively or postoperatively. Fifteen patients were found to have abnormality prior to operation. Their predominant abnormality was low antithrombin III activity. Sixty-one patients became hypercoagulable postoperatively. Predominant abnormality in this group of patients was increased thrombin generation and increased platelet adhesiveness. Evaluation of patients in this study group revealed a decrease in the incidence of pulmonary embolism, an increase in the patency of vein grafts, and the elimination of anticoagulant therapy in 24 percent of the patients.

A comparison of patients with endoscopic esophageal perforations and patients with Boerhaave's syndrome.

A review was conducted to ascertain whether patients who suffered spontaneous postemetic esophageal rupture (Boerhaave's syndrome) experienced higher morbidity and mortality than patients who had endoscopic iatrogenic esophageal perforations. Review of the records of three medical centers from 1960 to 1985 identified 11 patients with Boerhaave's syndrome (group B) and 19 with iatrogenic perforations (group E). In group B, four patients were diagnosed greater than 24 h after perforation. Nine were treated surgically; of these one died. Two group B patients who were treated conservatively survived. In group E, only four patients were diagnosed greater than 24 h after perforation. Of 19 patients, 15 were treated surgically and four, medically. In group E, three patients died (one surgically and two conservatively treated). This study suggests that there is little difference in mortality between the two groups of patients as long as the diagnosis is made early and therapy is instituted promptly.

The use of computed tomography in the evaluation of mediastinal masses.

A retrospective analysis was conducted to ascertain whether computed tomography had increased diagnostic accuracy while decreasing the number of tests needed in the preoperative assessment of patients with mediastinal masses. A total of 42 patients were entered into the study: Fifteen patients were evaluated before the advent of computed tomography (No CT) and 27 patients had computed tomography during their evaluation (CT). The No CT group comprised 10 male and five female patients (2:1 ratio); the age range was 8 months to 61 years. The CT group included 15 male and 12 female patients (1.25:1.0 ratio), the age range being 21 to 70 years. In each group, both invasive and noninvasive studies were done. Although the CT group had 40 noninvasive tests, 27 were computed tomographic scans. The additional 13 noninvasive tests and the five invasive tests added no significant diagnostic information. In the No CT group, preoperative evaluation as to the cystic or solid nature of the mass was correct only four of 13 times (31%). In the CT group, 22 of 25 patients had accurate assessment as to the cystic or solid nature of the lesions (88%). In addition, extension of the mass into other structures, consistent with malignancy, was correctly diagnosed preoperatively in nine of the patients in the CT group. Two had extension of the mass at operation not preoperatively diagnosed (82% accuracy). None of the No CT group was given an assessment of possible mass extension preoperatively. The results suggest that mediastinal masses can be evaluated by computed tomography with a high degree of accuracy for predicting the nature, size, location, and involvement of other organs by the mass. The use of other tests before resection generally yields little additional information.

Coagulation factors influencing thrombosis of aorta-coronary bypass grafts.

Thirty patients in whom all aorta-coronary artery vein grafts became occluded within one year of operation, as demonstrated by cardiac catheterization, were evaluated for hypercoagulability. A total of 59 grafts were constructed in these patients. At operation, blood flows of 35 to 90 c.c. per minute were measured through the grafts. In 23 of the 30 patients, the blood was to be hypercoagulable, as evidenced by a low level of antithrombin III activity, high thrombin generation index, high factor VII values, or high platelet adhesivity. Another group of 11 patients (total number of grafts, 23) had all grafts patent at cardiac catheterization. These patients had flows through the grafts ranging from 20 to 125 c.c. per minute. None of the patients with patent grafts had hypercoagulable blood. The status of runoff was comparable between the patients with open grafts and those with occluded grafts.

Routine operative arteriography during carotid endarterectomy: a reassessment.

One hundred and thirty-one consecutive operative arteriograms done in conjunction with carotid endarterectomy are reported. Radiographically obtrusive defects were found in 5.3% of arteriograms, with 1.5% in the common carotid artery, 2.3% in the external carotid artery, and 1.5% in the internal carotid artery. Potential complications were introduced by the operative arteriograms in 2.3% of the patients. One patient developed a persistent hemiparesis thought to be related directly to the performance of the arteriogram. On the basis of this review, routine operative arteriography as an adjunct to carotid endarterectomy has been discontinued at out institution. Specific indications for obtaining operative arteriograms are outlined.

Fibromuscular dysplasia of the internal carotid arteries.

Seven patients with fibromuscular dysplasia of the internal carotid arteries have been operated upon at Walter Reed Army Medical Center. One lesion was treated by graduated dilatation with Bake's dilators combined with resection, end-to-end anastomosis, and vein patching of a tortuous segment. All other lesions were treated by graduated dilatation with an arterial dilator-shunt. All of these patients are asymptomatic presently. One patient has been operated upon recently because of symptoms related to the previously unoperated side as well as mild symptoms related to the previous operation. Two other patients with arteriographic evidence of fibromuscular dysplasia are being followed clinically. One is asymptomatic and one has minimal symptoms. Both are being treated with acetylsalicylic acid in hopes of preventing microembolization from these lesions. Important technical considerations in treating this condition are meticulous dissection of the internal carotid artery as near to the base of the skull as possible, confining the arteriotomy to the region of the carotid bulb, and straightening the carotid artery while passing the dilator under direct vision. A technique for routine shunting in these patients now is available.

Traumatic arteriovenous fistulas and false aneurysms: a review of 558 lesions.

Through the Vietnam Vascular Registry which was established in 1966 at Walter Reed Army Medical Center, copies of medical records of 509 combat casualties with 558 arteriovenous fistulas and false aneurysms have been analyzed. This represents approximately 7 percent of the vascular injuries in American casualties from Southeast Asia, from 1963 to 1972, which are included in the Registry effort. Contributions of several hundred individuals are included in this documentation, however, more than one fourth of the patients, 149 or 29.3 percent, have been evaluated in our clinic. There were 296 false aneurysms and 262 arteriovenous fistulas. Multiple lesions occurred in 7.9 percent of the casualties. Fragment wounds accounted for 487 or 87.3 percent of the lesions with 85.5 percent in extremity vessels. Early recognition and definitive surgical treatment usually were accomplished: 52.8 percent within the first 30 days following injury. Ligation was either accepted or required in about 50 percent of the lesions. The mortality rate was 1.8 percent and the morbidity associated with the vascular injury was 6.3 percent. There were eight amputations for an amputation rate of 1.7 percent. Potential complications of heart failure, proximal arterial dilatation, and endocarditis were essentially absent.

Asymptomatic cervical bruit and abnormal ocular pneumoplethysmography: a prospective study comparing two approaches to management.

Fifty-seven patients with cervical bruits and abnormal ocular pneumoplethysmography but without symptoms were followed prospectively. Mean follow-up was 32 months and all patients were followed for at least 1 year. Twenty-nine patients consented to join a randomized study comparing treatment with aspirin, close follow-up, and no intervention unless symptoms developed [( NI: ASA] n = 14) versus intervention with arteriography and prophylactic surgery [( I: A/S] n = 15). Among patients who refused randomization, 14 were treated with NI: ASA and 14 with I: A/S. Endpoints for analysis included all unfavorable outcomes related to both management plans and included stroke, death of stroke, major angiographic and perioperative complications, asymptomatic carotid occlusion, and recurrent carotid artery stenosis. In both the randomized and nonrandomized portions of the study unfavorable outcomes were more frequent in patients treated with I: A/S, and by combining the results of both studies a significant difference was observed (N: ASA - 3.6% versus I: A/S - 31%; X:2 = 4.78; p less than 0.05). Among patients treated with NI: ASA, a single minor stroke occurred without warning. In patients from all groups who underwent arteriography, advanced carotid stenosis was found in 78% (mean percent diameter stenosis = 72% +/- 2%; mean residual lumen = 1.3 +/- 0.1 mm). We conclude that, despite the probability of underlying severe carotid stenosis, most patients with cervical bruit and abnormal ocular pneumoplethysmography but without symptoms are appropriately managed without intervention unless symptoms develop.

Saccular renal artery aneurysm as a cause of hypertension.

The case of a patient with renovascular hypertension related to an arterial kink is reported. The arterial kink was caused by a renal artery aneurysm and was not apparent with angiography. This is the first reported case in which renin-mediated hypertension was clearly related to a correctable mechanical problem from a saccular renal artery aneurysm. Indications for surgical repair of renal artery aneurysms and angiographic findings indicative of a functionally significant renal artery stenosis are reviewed.

Failure of immunosuppression to prolong venous allograft survival.

The role of allograft veins in vascular reconstruction remains ill defined. The present experiment was undertaken to evaluate the role of immunosuppression in maintaining allograft patency in the canine femoral venous circulation. Twenty-seven mongrel dogs had segments of both femoral veins excised and each dog received one allograft and one autograft. The dogs were randomly assigned to a control group or to one of three treatment regimens of azathioprine. Low doses of azathioprine were of no benefit in improving patency of venous alografts. Microscopic evaluation of these grafts suggests that substantial intimal repopulation by host cells occurs by six to eight weeks in the canine model. Other methods of preserving patency until intimal repopulation occurs deserve further investigation.

Staged aortofemoropopliteal revascularization.

Staged proximal and distal revascularization may be required in some patients with combined aortoiliac and femoropopliteal disease due to inadequacy of the profunda femoris artery or distal popliteal arterial disease. When these situations arise, one may expect that the procedures may be performed with very low morbidity (10% in this series) and mortality (0.0% in this series). Moreover, one may expect satisfactory results in most cases. In our series of 20 patients, 72.7% of extremities undergoing distal revascularization after previous proximal revascularization remain improved with over three years' follow-up.

Complex cerebral revascularization.

Although carotid endarterectomy is the usual technique for treating symptoms related to extracranial arterial occlusive disease, cerebrovascular and upper extremity symptoms caused by lesions of the innominate, common carotid, or subclavian orifices necessitate more complex revascularization techniques. We have treated five patients, three females and two males, with symptoms of cerebrovascular and/or upper extremity ischemia by highly individualized, complex, revascularization techniques. The procedures were amalgamations of carotid-subclavian bypass, carotid-subclavian bypass with carotid bifurcation endarterectomy, subclavian-subclavian bypass, axillo-axillary bypass, and carotid-axillary bypass. The conditions of all patients were greatly improved and four of the five patients became asymptomatic. These procedures seem to be highly effective in relieving symptoms and they minimize the risks of cerebral and upper extremity revascularization.

Doppler cerebrovascular examination, oculoplethysmography, and ocular pneumoplethysmography use in detection of carotid disease: a prospective clinical study.

To determine the comparative acccuracy of three noninvasive cerebrovascular testing systems, 72 patients underwent complete evaluation by Doppler cerebrovascular examination (DCE), oculoplethysmography (OPG-Kartchner), ocular pneumoplethysmography (OPG-Gee), and angiography. Considering 60% diameter stenosis or more by angiography as a true positive finding, the noninvasive tests of the 72 patients showed the following results: DCE, two false-positive, 17 false-negative, and 53 correct with an overall accuracy of 74%; OPG-Kartchner, six false-positive, four false-negative, and 62 correct with an overall accuracy of 86%; and OPG-Gee, no false-positive, two false-negative, and 70 correct with an overall accuracy of 97%. Independent of noninvasive test results, 57 symptomatic and three asymptomatic patients were selected for carotid endarterectomy. Of these 60 patients, 55 (92%) had positive preoperative OPG-Gee tracings. Noninvasive testing is a valuable carotid endarterectomy. Although considerable carotid ulceration may be undetected by noninvasive study, it was uncommon in this series.

Coagulation abnormalities in patients with arterial, venous, and combined arterial and venous thromboses.

Thrombotic disorders are much more common than hemorrhagic disorders. Nonetheless, most knowledge of coagulation relates to the hemorrhagic disorders. We have done extensive coagulation evaluations in patients with arterial thromboses only, venous thromboses only, and in patients with combined arterial and venous thromboses. Prominent abnormalities in platelet aggregation, factors VIII, IX, and XI levels, and fibrinogen were noted in all groups. These types of studies should eventually lead to a fuller understanding of thrombotic disorders.

Heparin. Efficacy and safety after arterial operations.

Hemorrhage is the most serious side effect of heparin sodium use. Under several circumstances, one may need to administer heparin to patients who have had recent peripheral vascular operations. Avoiding an inordinate number of hemorrhagic complications is mandatory after such operations. Side effects appear to be minimized by administering heparin by continuous intravenous (IV) infusion. Nineteen patients with recent peripheral vascular operations were given heparin by continuous IV infusion. A known hemorrhagic complication developed in only one. The degree of hemorrhage was mild and did not necessitate cessation of treatment with heparin. None of the patients whose mean activated partial thromboplastin times were in the therapeutic range experienced thrombotic complications while receiving heparin.

Popliteal vascular entrapment. Its increasing interest.

In the past 20 years since the first clinical management of a patient with a congenital anomaly associated with an abnormal medial head of the gastrocnemius muscle causing external compression on the popliteal artery, approximately 100 similar lesions have been documented in the world's literature. This has been a lesion of international interest, with only approximately 25% of the cases from hospitals in the United States. This present series of 14 lesions from Walter Reed Army Medical Center, Washington, DC, during a 12 1/2-year period beginning in September 1966 emphasizes the increasing interest in this lesion. The young athletic male in whom intermittent claudication develops with strenuous exercise or the middle-aged patient with a popliteal aneurysm should be evaluated for the possibility of popliteal vascular entrapment. Medial deviation of the popliteal artery seen angiographically is a classic finding, however, there might also be segmental occlusion of the midpopliteal artery. This series outlines various types of popliteal vascular entrapment and documents successful surgical management.

Hypercoagulability in patients with peripheral vascular disease.

Twenty-seven patients with peripheral vascular disease had studies of thrombin generation, antithrombin III -alues, factor VIII values, platelet adhesitivity, and activated partial thromboplastin time. Of the studies performed, the thrombin generation index, antithrombin III values, and, to a lesser extent, activated partial thromboplastin time were reliable in confirming clinically suspected hypercoagulability. When patients were placed into groups with and without operative complications, it was noted that the group with operative complications had higher average values of thrombin generation index and lower average values of antithrombin III and activated partial thromboplastin time than did the group without operative complications. It is thought that these tests may be useful in selecting those patients with a high risk of thrombotic complications from vascular surgery and who may benefit from anticoagulant management while undergoing necessary vascular reconstructive procedures.

Coverage of exposed vascular conduits.

When a vascular conduit becomes exposed, it is generally thought that if it is not already infected, it will soon become so. The most comprehensive treatment would be removal of the prosthesis, debridement of the wound, and extraanatomic bypass. Occasionally, however, extraanatomic bypass cannot be done. In such cases, local measures, such as skin grafting or skin flap coverage, may be used. Our two cases illustrate that these procedures can, on occasion, provide long-term coverage of exposed vascular conduits.

Anastomotic aneurysms.

Although the incidence of anastomotic false aneurysms decreased precipitously with the cessation of usage of silk sutures for vascular anastomoses, the prevalence of these aneurysms has undoubtedly increased in keeping with an ever-increasing volume of peripheral vascular operations. Most aneurysms occur at femoral anastomoses and are easily diagnosed, since most patients present with a groin mass. Anastomotic aneurysms cannot be considered innocuous. Some may rupture and others have been associated with limb ischemia due to acute thrombosis or embolism. Thus, surgical correction is indicated for most anastomotic aneurysms. Patients at high risk with small aneurysms in accessible locations may, however, be followed if they are asymptomatic and there is no evidence of enlargement of the aneurysm [5].