Aortic Arch Morphology and Aortic Length in Patients with Dissection, Traumatic, and Aneurysmal Disease.

OBJECTIVES: To assess aortic arch morphology and aortic length in patients with dissection, traumatic injury, and aneurysm undergoing TEVAR, and to identify characteristics specific to different pathologies. METHOD: This was a retrospective analysis of the aortic arch morphology and aortic length of dissection, traumatic injury, and aneurysmal patients. Computed tomography imaging was evaluated of 210 patients (49 dissection, 99 traumatic injury, 62 aneurysm) enrolled in three trials that received the conformable GORE TAG thoracic endoprosthesis. The mean age of trauma patients was 43 ± 19.6 years, 57 ± 11.7 years for dissection and 72 ± 9.6 years for aneurysm patients. A standardized protocol was used to measure aortic arch diameter, length, and take-off angle and clockface orientation of branch vessels. Differences in arch anatomy and length were assessed using ANOVA and independent t tests. RESULTS: Of the 210 arches evaluated, 22% had arch vessel common trunk configurations. The aortic diameter and the distance from the left main coronary (LMC) to the left common carotid (LCC) were greater in dissection patients than in trauma or aneurysm patients (p < .001). Aortic diameter in aneurysm patients was greater compared with trauma patients (p < .05). The distances from the branch vessels to the celiac artery (CA) were greater in dissection and aneurysm patients than in trauma patients (p < .001). The take-off angle of the innominate (I), LCCA, and left subclavian (LS) were greater, between 19% and 36%, in trauma patients than in dissection and aneurysm patients (p < .001). Clockface orientation of the arch vessels varies between pathologies. CONCLUSIONS: Arch anatomy has significant morphologic differences when comparing aortic pathologies. Describing these differences in a large sample of patients is beneficial for device designs and patient selection.

The PARP inhibitor ABT-888 potentiates dacarbazine-induced cell death in carcinoids.

Monoagent DNA-alkylating chemotherapies like dacarbazine are among a paucity of medical treatments for advanced carcinoid tumors, but are limited by host toxicity and intrinsic chemoresistance through the base excision repair (BER) pathway via poly (ADP-ribose) polymerase (PARP). Hence, inhibitors of PARP may potentiate DNA-damaging agents by blocking BER and DNA restoration. We show that the PARP inhibitor ABT-888 (Veliparib) enhances the cytotoxic effects of dacarbazine in carcinoids. Two human carcinoid cell lines (BON and H727) treated with a combination of ABT-888 and dacarbazine resulted in synergistic growth inhibition signified by combination indices <1 on the Chou-Talalay scale. ABT-888 administered prior to varying dacarbazine doses promoted the suppression of neuroendocrine biomarkers of malignancy, ASCL1 and chromogranin A, as shown by western analysis. Ataxia telangiectasia mitogen factor phosphorylation and p21Waf1/Cip1 activation, indicative of DNA damage, were increased by ABT-888 when combined with dacarbazine treatment, suggesting BER pathway attenuation by ABT-888. PE Annexin V/7-AAD staining and sorting revealed a profound induction of apoptosis following combination treatment, which was further confirmed by increased PARP cleavage. These results demonstrate that ABT-888 synergizes dacarbazine treatment in carcinoids. Therefore, ABT-888 may help treat carcinoids unresponsive or refractory to mainstay therapies.

Focal cerebral ischemia in rats: effects of induced hypertension, during reperfusion, on CBF.

The effect of phenylephrine-induced hypertension on CBF was investigated after 120 min of middle cerebral artery occlusion in rats. Blood pressure was manipulated by one of the following schedules during a 90-min period of reperfusion: 90/NORM, 90 min of normotensive reperfusion; 90/HTN, 90 min of hypertensive reperfusion (MABP increased by 30 mm Hg); or 15/HTN, the 90-min period of reperfusion was divided into 30 min of normotension, followed by 15 min of hypertension and 45 min of normotension. At the end of reperfusion, 100 microCi kg-1 of [14C]iodoantipyrine was given and an autoradiographic analysis of CBF performed. In the coronal brain section at the center of middle cerebral artery distribution, the area (percentage of hemisphere, mean +/- SD) with a CBF of 0-20 or 21-40 ml 100 g-1 min-1 was less (p less than 0.05) in the 15/HTN group (1 +/- 2 and 5 +/- 3%, respectively) versus the 90/HTN group (12 +/- 4 and 10 +/- 4%), which was in turn less than in the 90/NORM group (18 +/- 5 and 22 +/- 6%). These data are consistent with the hypothesis that during reperfusion a short interval of hypertension effectively augments CBF via an abrupt opening of collapsed vessels and that a more sustained interval of hypertension conveys no added benefit.

Development of echogenic, plasmid-incorporated, tissue-targeted cationic liposomes that can be used for directed gene delivery.

RATIONALE AND OBJECTIVES: Echogenic antibody-conjugated anionic liposomes have been developed that allow directed tissue targeting and acoustic enhancement. These are not efficient for gene delivery. A cationic formulation that allows directed gene delivery while retaining acoustic properties may provide more efficient transfection. METHODS: Cationic liposomes were prepared and acoustic reflectivity was determined. Anti-fibrinogen-conjugated liposomes were laid on fibrin-coated slides and adherence was quantified using fluorescence techniques. Liposomes were combined with a reporter gene and plated on cell cultures. Human umbilical vein endothelial cells were stimulated to upregulate intercellular adhesion molecule-1 (ICAM-1) and were treated with anti-ICAM-1-conjugated liposomes, and gene expression was quantified. RESULTS: Cationic liposomes retained their acoustic reflectivity and demonstrated specific adherence to fibrin under flow conditions. Significant transfection of human umbilical vein endothelial cells was demonstrated, with higher gene expression seen with specific antibody-conjugated liposomes. CONCLUSIONS: Novel acoustic cationic liposomes have been developed that can be antibody conjugated for site-specific adherence and directed cell modification. This presents exciting potential for a vector that allows tissue enhancement and targeted gene delivery.

Gastrointestinal tract complications after acute spine injury.

OBJECTIVES: To determine the incidence, risk factors, and mortality rate of gastrointestinal complications in patients with acute spine injury and to derive methods by which mortality can be reduced. DESIGN: Case series. SETTING: Regional tertiary care center. PATIENTS: Consecutive sample of 1952 patients with acute spine injury with complete medical records who were admitted from 1981 through 1990. MAIN OUTCOME MEASURES: Gastrointestinal tract complications, age, sex, time from injury to admission, cause of injury, level of spine injury, neurologic deficit, head injury, injury to other organ systems, incidence of surgical intervention for spine injury, length of hospital stay, and mortality rate. RESULTS: The incidence of gastrointestinal complications was 1.9%. Gastrointestinal hemorrhage was the most frequent complication. Risk factors for gastrointestinal complications were increasing age (P < .02), male sex (P < .01), injury to other organ systems (P < .02), head injury (P < .02), cervical spine injury (P < .02), and neurologic deficit (P < .005). The mortality rate was 19% in patients with gastrointestinal complications, significantly greater (P < .005) than the 2.9% rate in patients without gastrointestinal complications. CONCLUSIONS: Gastrointestinal complications after acute spine injury are uncommon but frequently lethal. Prophylaxis against hemorrhage and earlier diagnosis and surgical intervention are recommended.

Natural history of composite sequential bypass: ten years' experience.

BACKGROUND: We previously reported 48-month patency rates of composite sequential bypass (CSB) approaching 60%. Yet, extended patency and limb salvage rates are unknown. HYPOTHESIS: Long-term patency and limb salvage rates of CSB are affected by sex, bypass configuration, and warfarin therapy. DESIGN: Medical records of all patients who underwent CSB during a 10-year period were retrospectively reviewed. SETTING: A referral center for the Chicago, Ill, region. PATIENTS: One hundred consecutive patients (mean age, 68.8 years; 57% were men and 49% had diabetes) undergoing 102 CSBs for limb salvage (ulcer, 43%; rest pain, 39%; and gangrene, 18%) from January 1986 to January 1996 were identified. INTERVENTIONS: Warfarin was used after surgery by 72% of patients and aspirin was used by the remainder of them. MAIN OUTCOME MEASURES: Life table primary patency and limb salvage rates were compared for sex, diabetes mellitus status, location of distal prosthetic anastomosis (above knee vs. below knee), and anticoagulation drug therapy (warfarin sodium vs aspirin) with log-rank statistics. RESULTS: Primary patency of CSB was 56% at 24 months, 29% at 48 months, and 20% at 84 months (SE <10%; mean follow-up, 19.6 months [range, 1.0-110.0 months]). Limb salvage rates were 64% at 24 months, 30% at 48 months, and 23% at 84 months (SE <10%); 66% and 90% of patients had failed grafts requiring amputation by 3 months and 1 year, respectively. CONCLUSIONS: Composite sequential bypass for limb salvage provides reasonable 2-year patency. However, patency rates steadily declined from year 2 to year 5. After CSB failure, limb salvage rates are poor, with 90% of patients progressing to amputation within 1 year.

Postoperative radiotherapy for squamous cell carcinoma of the maxillary sinus: analysis of local control and late complications.

This retrospective study was conducted to analyze the local control and late complications in patients with squamous cell carcinoma of the maxillary sinus treated with postoperative radiation therapy following surgery. Between 1979 and 1998, 41 patients with squamous cell carcinoma of the maxillary sinus were treated with postoperative irradiation following partial or total maxillectomy. Tumor classification according to the TNM classification of the International Union Against Cancer (1997) was T2 in 6 patients, T3 in 21 patients, and T4 in 14 patients. Fourteen patients had negative surgical margins, 23 had microscopically positive margins, and 4 had grossly positive margins. Sixteen patients received preoperative intraarterial chemotherapy. The total dose to the primary tumor bed was 40-70 Gy (median: 54 Gy) with a fraction size of 2 Gy. The median follow-up time of the surviving patients was 93 months (range: 25-179 months). Local recurrence was observed in 17 patients (41%), and the 5-year actuarial overall survival and local control rates were 48% and 55%, respectively. In the univariate analysis, surgical margin status and total dose each had a statistically significant impact on local recurrence. For the patients with negative surgical margins, 8 of 9 (89%) patients achieved local control with a dose of 50-54 Gy, while 7 of 10 (70%) patients with microscopically positive margins achieved local control with a dose of 60-64 Gy. There were 11 late complications found in 9 patients; bone necrosis in 2, soft tissue necrosis in 2, trisumus: 2, cellulitis in 1, retinopathy in 1, and vision impairment in 3 patients. A total dose of 60 Gy or more was administered in all patients who suffered late complications except for 2 patients with vision impairment. These results indicated that an optimal dose of postoperative irradiation according to the surgical margin status was necessary to achieve local control for squamous cell carcinoma of the maxillary sinus following surgery. For patients with negative surgical margins, a total dose of 50-54 Gy in conventional fractionation was appropriate to achieve local control as well as to reduce late complications. On the other hand, a dose of 60 Gy or more was required for the patients with microscopic positive margins.

Early clinical results and studies of aortic aneurysm morphology after endovascular repair.

Endovascular repair is a feasible treatment alternative with favorable short-term results compared with standard operations. Nonrandomized, multicenter trials already in progress should help to define the role of endovascular grafting in the treatment of patients who are otherwise candidates for conventional repair. Long-term follow-up studies will test the durability of the procedure, including clinical repercussions of late endoleaks and migration related to slow alterations in aortic morphology, such as neck dilation and aortic shortening. More research is needed into long-term aortic morphologic changes; further insights into these changes may allow subclinical prediction of clinical events and permit intervention before a catastrophic failure. How great an advantage this procedure has over observation in high-risk patients for whom no open surgical alternative is available is also unknown because the overall mortality of this patient cohort may mitigate any treatment benefits. In today's cost-conscious world, the viability of this new technology may be dependent on balancing the short-term benefits of this procedure against its associated requirements for monitoring and subsequent reinterventions.

Filter placement by ultrasound technique at the bedside.

Vena cava filtration devices are commonly inserted for the prevention of fatal pulmonary emboli. Several imaging methods are used today to direct device placement. Bedside insertion has several advantages, particularly in the critically ill patient. Imaging techniques include bedside fluoroscopy, transperitoneal ultrasound, and intravascular ultrasound. We have now successfully placed 10 transfemoral vena cava filters by use of intravascular ultrasound at the patient's bedside. This appears to be a feasible method for filter insertion.

Anatomic changes after endovascular grafting for aneurysmal disease.

Long-term follow-up of controlled clinical trials of endovascular grafting for aortic aneurysms will provide data on the safety and efficacy of this new treatment to reduce morbidity and mortality compared with standard treatment. It will be several years before this information will be available, and careful analysis of surrogate markers for clinical success has value for predicting long-term outcome. One essential surrogate marker is aortic aneurysm diameter, which has traditionally been the most important variable in calculating rupture risk, and multiple studies have shown that aneurysms shrink after complete endovascular exclusion. Furthermore, measurements of aortic neck size and aortic length has shown interesting patterns that may affect the durability of endovascular repair and, thus, may suggest potential strategies for the design of future devices.

Screening and surveillance for abdominal aortic aneurysms: who needs it and when.

Early detection of abdominal aortic aneurysms potentially can save many lives by preventing aneurysm rupture. Screening programs, however, have yet to be proven as an efficient means of accomplishing this goal and improving overall life expectancy. Until more information is available, selective high-risk screening may be the only viable option. Recently, 2 large prospective studies have better defined the utility of screening programs and have provided guidelines for the safe nonoperative management of small aneurysms. Using ultrasound surveillance, these can be followed up at 3- to 12-month intervals, depending on their size, with operative intervention reserved for aneurysms that enlarge rapidly, become symptomatic, or reach 5.5 cm in diameter.

Hypervolemic-hemodilution and hypertension during temporary middle cerebral artery occlusion in rats: the effect on blood-brain barrier permeability.

The effect of hypervolemic-hemodilution, with and without hypertension, on blood-brain barrier permeability was investigated in rats, after 180 minutes of middle cerebral artery occlusion (MCAo), and 60 minutes of reperfusion. One of the following conditions was maintained during MCAo: 1) Control--hematocrit and blood pressure were not manipulated; 2) Hypervolemic-Hemodilution/Normotension--the hematocrit was decreased to 30%; 3) Hypervolemic-Hemodilution/Hypertension--the hematocrit was decreased to 30% and mean arterial pressure increased by 30 mmHg with phenylphrine. In all groups, Evans Blue was administered, and its concentration determined by spectrophotometric assay. Evans Blue (micrograms (g-1 of brain tissue [mean +/- SD]) was greater in the Hypervolemic-Hemodilution/Hypertension group (71 +/- 20) versus the Control (13 +/- 9) and Hypervolemic-Hemodilution/Normotension (17 +/- 10) groups (p less than 0.05). No other differences were present. These results support the hypothesis that during MCAo, hypervolemic-hemodilution/hypertensive therapy effects an increase in blood-brain barrier permeability in the early period of reperfusion.

Morphometric analysis of the popliteal artery for endovascular treatment.

This study intended to determine the precise diameter of the popliteal artery in patients at risk for popliteal aneurysms. Accurate sizing is necessary to develop devices for endovascular treatment of popliteal aneurysms. Fifty-four patients with abdominal aortic aneurysms (AAAs) had computed tomography (CT) scans of the popliteal arteries. Age- and gender-matched control subjects were measured by ultrasound. NIH Image was used to measure the minor diameter at the adductor hiatus (proximal) and femoral condyles (midpopliteal artery). There were 4 unsuspected popliteal aneurysms (7.4%). The proximal popliteal artery was ectatic in these patients: 13.4 +/- 5.2 mm. Proximal and midpopliteal arteries were significantly larger in the other patients with AAAs compared with controls: 9.6 +/- 1.8 mm vs 7.9 +/- 1.1 mm at the hiatus (p<0.001) and 10.2 +/- 2 mm vs 7.9 +/- 0.9 mm at the condyles (p<0.001). The popliteal artery was focally larger in patients with AAAs without popliteal aneurysms. The popliteal artery was larger in men compared with women; 9.8 +/- 1.8 mm vs 8.8 +/- 1.9 mm at the hiatus (p=0.024) and 10.5 +/- 1.9 mm vs 9.0 +/- 2.4 mm at the condyles (p=0.005). The proximal popliteal artery was 2 mm larger in patients at risk for popliteal aneurysms and 5 mm larger in patients with popliteal aneurysms compared to controls. Focal ectasia of the midpopliteal artery was common. Planning for endovascular treatment of popliteal aneurysms must incorporate this striking enlargement.

[Genetic epidemiological approach to large bowel cancer].

Incidence of large bowel cancer under predominant genetic influence is estimated to occupy about one tenth of general large bowel cancer population. They are defined to include hereditary gastrointestinal polyposes (adenomatosis coli, Peutz-Jeghers syndrome and juvenile polyposis) and the non-polypotic familial (hereditary) large bowel cancer (Cancer Family Syndrome and allied conditions). The strategy for the genetic cancer high-risk group under these conditions based on the central registration system was described. Our experiences indicated the approach was actually effective for the polyposes a and was also promising for the non-polyposis familial of large bowel cancer.

[High tissue concentration of 5-FU reduced local recurrence after administration of tegafur suppositories].

Forty-two patients with head and neck cancer were treated with tegafur suppository for 7 days preoperatively and clinical value of this treatment was assessed. In a group which indicated tumor tissue concentrations of 5-FU were more than 0.5 micrograms/g, local recurrence decreased in the period of postoperative observation for 42 months. A survival rate of this group was better than others. From these results, preoperative tegafur suppository treatment seemed to have a role in expectation of improvement of local control in head and neck cancer therapy.

[Studies on the effect of lentinan on human immune system. II. In vivo effect on NK activity, MLR induced killer activity and PHA induced blastic response of lymphocytes in cancer patients].

Immunological activities of lymphocytes were studied in patients with cancer of digestive organs and mamma after administration of lentinan. When 11 cancer patients received lentinan i.v. 2 mg, NK activity of lymphocytes was increased in 4 patients on the following day. With the same condition, MLR induced killer activity against Raji cell of lymphocytes was increased in 3/7 patients and PHA response was also increased in 3/7 patients. These activities were returned to values before the administration of lentinan. Then each activity was examined after administration of lentinan twice a week. NK activity, MLR induced killer activity and PHA response were increased in 4/15, 8/12 and 5/11 patients, respectively.

[Maximum tolerated dose of tegafur in rats].

Maximum Tolerated Dose of Tegafur was estimated by per-oral administration in male Donryu rats. Tegafur was administered for 24 weeks at respective doses of 90 mg, 120 mg and 150 mg/kg/day. Six of 10 (60%) died during the treatment in those groups administered with 120 mg and 150 mg/kg/day, respectively. The cause of death of these rats was severe pneumonia. All 10 of the group given 60 mg/kg/day survived until end of the administration and were sacrificed for histological examination of organs. These rats showed apparent suppression of body weight gain compared with controls (p less than 0.001). Slight inflammation of the lungs was observed in all rats, congestion of the liver and local degeneration and necrosis of the liver cells in a few rats and cellular degeneration of bone marrow in one rat. There was no remarkable change in the digestive tract, kidney, thymus or reproductive organs. Accordingly, the Maximum Tolerated Dose of Tegafur was determined to be 90 mg/kg/day.