Embolization of uterine arteriovenous malformations associated with cyanotic congenital heart disease.

Uterine arteriovenous malformation (AVM) is a rare cause of vaginal bleeding and miscarriage. We report two cases of uterine AVMs in patients with a history of complex congenital heart disease, an association that has not been previously described. Both patients were treated by selective uterine artery embolization, a minimally invasive therapy that has revolutionized the management of uterine AVMs, thus offering an alternative to conventional hysterectomy.

Phase I study of percutaneous cryotherapy for colorectal liver metastasis.

BACKGROUND: The aim was to determine the safety and feasibility of percutaneous cryotherapy for treating irresectable colorectal liver metastases. METHODS: Liquid nitrogen cryoprobes were inserted percutaneously into metastases using the Seldinger technique under computed tomographic guidance. Single-probe treatments were performed with either 3.6- or 6.3-mm cryoprobes (ice-ball volumes 18 and 59 cm3 respectively), or dual-probe treatments with two adjacent 6.3-mm probes (ice-ball volume 205 cm3). Treatment involved a single freeze--thaw cycle. RESULTS: Fifteen patients received 25 single-probe treatments and seven patients received 14 dual-probe treatments. The treatment-related mortality rate was zero and complications occurred after six of 39 treatments. Liver metastasis growth was significantly delayed for 2 months after dual-probe but not single-probe treatment. Metastasis cryotherapy stimulated an immediate rise, followed by a fall, in serum carcinoembryonic antigen (CEA) level, associated with immune upregulation that was significantly greater after dual-probe treatments. CONCLUSION: Ablation zones that were approximately four times larger than those produced by previously described percutaneous techniques delayed the growth of metastases, reduced serum CEA concentration, and induced detectable inflammatory and T-lymphocyte responses. Percutaneous cryotherapy for treatment of colorectal liver metastases is feasible and may have a place in conjunction with chemotherapy.

Treatment of iatrogenic femoral artery pseudoaneurysms using ultrasound-guided injection of thrombin.

AIM: To evaluate the use of ultrasound-guided percutaneous injection of thrombin for treatment of femoral artery pseudoaneurysms. METHOD: Nine patients with a confirmed femoral false aneurysm were included in the study. 0.5-1 ml of a 2000 U/ml solution of activated bovine thrombin was injected under ultrasound visualization into the neck of the aneurysm to induce thrombosis. The parent artery and adjacent major vessels were checked during and after the procedure to exclude propagation of thrombus. A check ultrasound examination was undertaken on the following day. RESULTS: Eight patients were successfully treated by a single injection. One patient required a second injection due to recurrence of their pseudoaneurysm 4 days after the initial treatment. The procedure was well tolerated in all cases and no complications were encountered. CONCLUSION: This small series provides further evidence that ultrasound-guided thrombin injection is a promising new method for the treatment of femoral false aneurysms.Hughes, M. J. et al. (2000). Clinical Radiology55, 749-751.

Uterine fibroleiomyoma: MR imaging appearances before and after embolization of uterine arteries.

PURPOSE: To evaluate the magnetic resonance (MR) imaging appearances of uterine fibroleiomyoma before and after embolization and to determine whether there are preembolization MR imaging characteristics that are predictive of a successful outcome. MATERIALS AND METHODS: MR imaging was performed in 18 patients (32 fibroleiomyomas) before and at 2 and 6 months after embolization of the uterine arteries. On each occasion, fibroleiomyoma signal intensity and gadolinium enhancement characteristics were assessed in comparison with those of myometrium on T1-weighted and gadolinium-enhanced images or with those of skeletal muscle on T2-weighted images. Fibroleiomyoma volume was measured by using the ellipsoid formula. RESULTS: The mean fibroleiomyoma volume before embolization was 340 cm3 (range, 15-1,383 cm3). The mean reduction in fibroleiomyoma volume was 43% at 2 months and 59% at 6 months. Before embolization, high signal intensity on T1-weighted images was predictive of a poor response (P = .008), and high signal intensity on T2-weighted images was predictive of a good response (P = .007). The degree of gadolinium enhancement was not correlated with fibroleiomyoma volume reduction (P = .46). CONCLUSION: MR imaging was useful for evaluation of changes in fibroleiomyoma volume after uterine arterial embolization. MR imaging characteristics of fibroleiomyomas before embolization can help predict subsequent response to treatment.

Effects of the lazaroid, tirilazad mesylate, on sepsis-induced acute lung injury in minipigs.

OBJECTIVE: To assess the effects of the lazaroid, tirilazad mesylate, a potent lipid peroxidation inhibitor, in an animal model of Pseudomonas sepsis. DESIGN: Comparison of four experimental groups: a) saline control; b) Pseudomonas sepsis control; c) tirilazad mesylate control; and d) sepsis with tirilazad mesylate pre treatment. SETTING: University animal laboratory. SUBJECTS: Hanford minipigs (20 to 25 kg), anesthetized with pentobarbital and mechanically ventilated on an FIO2 of 0.4. INTERVENTIONS: Sepsis was induced by infusing Pseudomonas aeruginosa at 1 x 10(6) colony-forming units/kg/min over 120 mins. The tirilazad mesylate-treated group received a 5-mg/kg bolus 30 mins before, and a 3-mg/kg bolus 3 hrs after, the onset of sepsis. Hemodynamics, PaO2, and neutrophil counts were measured for 6 hrs. Thiobarbituric acid reactive material (TBARM) in tissue (lung, liver, and intestine), lung wet/dry weight ratio, lung myeloperoxidase activity, plasma tumor necrosis factor (TNF)-alpha concentrations, protein content, and percent neutrophils in bronchoalveolar lavage fluid were evaluated at the time the animals were killed (6 hrs). MEASUREMENTS AND MAIN RESULTS: Sepsis induced significant systemic hypotension, pulmonary hypertension, hypoxemia, and neutropenia. Sepsis also significantly increased TBARM content, lung wet/dry weight ratio, myeloperoxidase activity, plasma TNF-alpha concentrations, and bronchoalveolar lavage neutrophil percentage. Treatment with tirilazad mesylate significantly attenuated hypoxemia and decreased TBARM content, lung wet/dry weight ratio, myeloperoxidase activity, bronchoalveolar lavage protein, and bronchoalveolar lavage neutrophil percentage, but did not affect sepsis-induced hemodynamics, including systemic hypotension and pulmonary hypertension, plasma TNF-alpha concentrations, or neutropenia. CONCLUSIONS: Pretreatment with the tirilazad mesylate did not change P. aeruginosa sepsis-induced hemodynamic consequences. However, tirilazad mesylate attenuated sepsis-induced acute lung injury.

Abdominal radical trachelectomy: a new surgical technique for the conservative management of cervical carcinoma.

Traditionally radical hysterectomy has formed the mainstay of treatment for early stage cervical carcinoma. More recently radical trachelectomy and laparoscopic lymphadenectomy have been introduced to allow preservation of fertility. We present a new approach to fertility-sparing surgery, namely abdominal radical trachelectomy. The technique is similar to a standard radical hysterectomy and lymphadenectomy. In our technique the ovarian vessels are not ligated and, following lymphadenectomy and skeletonisation of the uterine arteries, the cervix, parametrium and vaginal cuff are excised. The residuum of the cervix is then sutured to the vagina and the uterine ateries re-anastomosed.

Antegrade catheterization of the brachial artery for embolizing a sarcoma of the forearm.

A case is described in which embolization of an alveolar soft part sarcoma, involving a forearm, was successfully achieved via cannulation of the brachial artery. The procedure was performed safely and more easily from this direct approach.

Objectively assessing nursing practices: a curricular development.

In preparation for the changing needs of undergraduate nursing students undertaking a Project 2000 degree, it was necessary to rethink the nursing skills programme. After studying the literature a nursing skills laboratory was designed which provided both an institutional and a domestic setting. A progressive programme was developed, to help the students learn nursing practices, which was based on the Objective Structured Clinical Evaluation (OSCE). A small pilot study was set up using second and third-year students from the traditional nursing studies degree. A number of stations were set up comprising various nursing scenarios. The students who were being assessed rotated through these. Other students acted as patients, examiners and some volunteered to be novices being taught by the more senior students. A set of marking criteria was drawn up for each station to enable each student to be assessed objectively. One of the stations was filmed to provide the students with personal feedback. By the end of the session the students had rotated through each of the stations and received the marked criteria as feedback. At the end of the session a focused group interview took place with all the students and the two lecturers involved in setting up the project. Students were positive and felt the process had potential for future development as a means of integration and consolidation of skills prior to clinical experience. The early introduction of filming to the programme was though to be of benefit by reducing stress levels through regular use. Students felt that the role of teaching the 'novice' helped them focus on their knowledge and performance. This process is resource intensive in human and non-human terms but enables small groups of students to learn in a realistic but safe, non-threatening environment and encourages them to take responsibility for their own learning.

The efficacy of percutaneous cholecystostomy in critically ill patients.

Percutaneous cholecystostomy (PC) has been proposed as a method of biliary decompression in critically ill patients with acute cholecystitis. We evaluated the efficacy of PC in this setting. The charts of 33 critically ill patients (mean age 52, range 5-87) who underwent PC for suspected acute cholecystitis were retrospectively examined. Univariate analysis was performed to identify which patients might benefit from PC. PC was technically successful in all patients with no direct mortality or major complications. Failure to improve within 24 hours was associated with increased mortality (P = 0.02). A total of 22/33 patients improved, 17/33 survived, and 8/33 required surgery. PC delayed definitive operation in two patients. Cholelithiasis was associated with surgical intervention (P = 0.01) but not increased mortality. Favorable prognosticators for survival included gallbladder dilatation (P = 0.01), pericholecystic fluid (P = 0.01), and absence of a pulmonary artery catheter (P = 0.02). Predictors of improvement included gallbladder nonvisualization on hepatobiliary scan (P = 0.047), positive bile cultures (P = 0.017), and initial drainage of < / = 100 cc (P = 0.009). Age, laboratory data, the use of total parenteral nutrition, and intubation did not predict outcome. Nine positive bile cultures prompted antibiotic changes in five cases. Finally, PC was less expensive than open cholecystostomy ($1620 versus $3155). PC is a safe, cost-effective, minimally invasive procedure that has diagnostic and therapeutic value in critically ill patients with acute cholecystitis. The involvement of a general surgeon is important to ensure that those patients who do not improve within 24 hours receive early surgical intervention and provide long-term definitive care for those patients with cholelithiasis.

Kinetic evaluation of lipophilic inhibitors of lipid peroxidation in DLPC liposomes.

The authors have developed a kinetic method that allows one to obtain relative reactivity constants for lipophilic antioxidants in free radical systems. Two experimental model systems were developed: (a) a methanolic solution using AMVN as the free radical initiator and linoleic acid as the substrate, and (b) a multilamellar vesicle system composed of dilinoleoylphosphatidylcholine and AAPH as the substrate and the initiator, respectively. The use of these two systems allows researchers not only to determine the intrinsic reactivity of a potential antioxidant, but also to evaluate its potency in a membranous system where the contribution of the physical properties of the antioxidant to the inhibition of lipid peroxidation is important. These results show that all antioxidants tested acted in these systems as free radical scavengers, and they validate the synergism between intrinsic scavenging ability and membrane affinity and/or membrane-modifying physical properties in the inhibition of lipid peroxidation.

Tirilazad mesylate protects stored erythrocytes against osmotic fragility.

The hypoosmotic lysis curve of freshly collected human erythrocytes is consistent with a single Gaussian error function with a mean of 46.5 +/- 0.25 mM NaCl and a standard deviation of 5.0 +/- 0.4 mM NaCl. After extended storage of RBCs under standard blood bank conditions the lysis curve conforms to the sum of two error functions instead of a possible shift in the mean and a broadening of a single error function. Thus, two distinct sub-populations with different fragilities are present instead of a single, broadly distributed population. One population is identical to the freshly collected erythrocytes, whereas the other population consists of osmotically fragile cells. The rate of generation of the new, osmotically fragile, population of cells was used to probe the hypothesis that lipid peroxidation is responsible for the induction of membrane fragility. If it is so, then the antioxidant, tirilazad mesylate (U-74,006f), should protect against this degradation of stored erythrocytes. We found that tirilazad mesylate, at 17 microM (1.5 mol% with respect to membrane lecithin), retards significantly the formation of the osmotically fragile RBCs. Concomitantly, the concentration of free hemoglobin which accumulates during storage is markedly reduced by the drug. Since the presence of the drug also decreases the amount of F2-isoprostanes formed during the storage period, an antioxidant mechanism must be operative. These results demonstrate that tirilazad mesylate significantly decreases the number of fragile erythrocytes formed during storage in the blood bank.

Variations in liver-colon anatomic relationship: relevance to interventional radiology.

PURPOSE: To determine the prevalence of significant variations in liver-colon anatomy in an unselected patient population and evaluate the potential effect of these variations on liver-related interventional procedures. PATIENTS AND METHODS: All abdominal computed tomographic (CT) scans were reviewed prospectively over a 4-month period. Cases that revealed variant hepatocolic anatomy were selected and analyzed for the position of the colon, gallbladder, and duodenum; liver morphology; and the anatomic relations of the right portal vein. RESULTS: Seventeen (3.3%) of 517 abdominal CT scans demonstrated variant hepatocolic anatomic relations. In seven cases, liver lobar morphology was normal, but the colon was interposed between the chest wall and the liver. The remaining 10 cases were characterized by hypoplasia or aplasia of one or both segments of the left lobe. In these cases the right portal vein was anteriorly exposed and was close to the gallbladder and transverse colon. In all 17 cases it was qualitatively judged that technical modifications might be needed in the performance of various interventional procedures, including percutaneous biliary drainage, biopsies, and transjugular intrahepatic portosystemic shunt creation. CONCLUSION: Variations in liver-colon anatomic relations in isolation or secondary to hepatic developmental anomalies may have a significant potential impact on the performance of various fluoroscopically guided hepatobiliary interventional procedures.

Iron-initiated tissue oxidation: lipid peroxidation, vitamin E destruction and protein thiol oxidation. Inhibition by a novel antioxidant, U-78517F.

Oxidative injury was initiated by addition of ferrous ammonium sulfate (FAS) to a suspension of whole rat brain homogenate in Krebs buffer. After FAS addition, tissue vitamin E dropped sharply over a 30-sec interval and then recovered marginally for 5 min. After 5 min, vitamin E levels dropped to a low and constant level. Also after 5 min, TBARS (thiobarbituric acid reactive substances, a color test for lipid peroxidation) showed a statistically significant (P < or = 0.05) increase that continued through the remainder of the 30-min experiment. Reduced protein thiols decreased significantly (P < or = 0.05) at 15 min post FAS addition. This suggests that, in this model of iron-initiated lipid peroxidation (LP), the endogenous antioxidant vitamin E is first depleted before membrane lipids and membrane bound proteins show evidence of oxidative injury. A novel antioxidant, U-78517F, inhibited the destruction of vitamin E, LP and protein thiol oxidation in this model. The efficacy of the compound after different times of addition is described.

Antioxidant effects in brain and spinal cord injury.

Oxygen radical-mediated lipid peroxidation appears to be a critical factor in posttraumatic neuronal degeneration. Thus, numerous studies have evaluated the neuroprotective efficacy of pharmacologic agents with lipid antioxidant activity in models of spinal cord and brain injury. Intensive pretreatment of animals with the endogenous lipid peroxyl radical scavenger alpha tocopherol (i.e., vitamin E) has been shown to decrease posttraumatic spinal cord ischemia and to enhance chronic neurologic recovery. However, the slow CNS tissue uptake of vitamin E requires chronic dosing, making it an impractical agent for the treatment of acute neural injury. The glucocorticoid steroid methylprednisolone has been shown to possess significant antioxidant efficacy and, when administered to animals or humans in antioxidant dosages, improves chronic neurologic recovery after spinal cord injury. This activity of methylprednisolone is independent of the steroid's glucocorticoid receptor-mediated actions. Novel antioxidant 21-aminosteroids have been developed that are devoid of glucocorticoid activity but have greater antioxidant efficacy than methylprednisolone. One of these, U74006F or tirilazed mesylate, has been shown to be effective in animal models of brain and spinal cord injury and is currently undergoing phase II clinical trials. Compounds that combine the amino functionality of the 21-aminosteroids with the peroxyl radical scavenging chromanol portion of vitamin E (i.e., 2-methylaminochromans) have also recently shown promise as neuroprotective agents. The consistent benefit afforded by antioxidant compounds adds further support to the concept that lipid peroxidation is an important therapeutic target for acute pharmacologic neuroprotection.

Effect of delayed administration of U74006F (tirilazad mesylate) on recovery of locomotor function after experimental spinal cord injury.

Beginning at either 30 minutes, 2 hours, 4 hours, or 8 hours after 180 g compression of the cat L2 spinal cord for 5 minutes, infusion of U74006F was initiated. In this series, the cats received a total U74006F dose of 5 mg/kg/48 hours. An additional group of injured cats was treated at 8 hours postinjury with a three-fold higher dose of U74006F (i.e., a total 48-hour dose of 15 mg/kg). Controls received an equal volume of vehicle (citrate-buffered saline) delivered over 48 hours. The cats were evaluated weekly for 4 weeks for recovery of overground locomotion based on an 11-point scale by an investigator blinded to the time and type (i.e., vehicle or drug) of material administered. By 4 weeks postinjury, there was no significant difference in the locomotor recovery of cats that received U74006F at either 30 minutes, 2 hours, 4 hours, or 8 hours after injury. However, only recovery in the groups treated at 30 minutes, 2 hours, or 4 hours after injury was significantly greater than vehicle-treated controls. Locomotor function in cats receiving either 5 mg/kg/48 hours or 15 mg/kg/48 hours of U74006F at 8 hours postinjury was not significantly different from that of the vehicle-treated animals. Mean (+/- SEM) 4-week recovery scores were 6.8 +/- 0.9, 5.9 +/- 1.0, 7.2 +/- 1.1, and 4.7 +/- 2.9 out of 11 for cats treated at 30 minutes, 2 hours, 4 hours, or 8 hours postinjury, respectively, with the 5 mg/kg/48 hour dose. The mean recovery score for cats treated at 8 hours after injury with the 15 mg/kg/48 hour dose was 3.4 +/- 1.8. The average score for the vehicle-treated controls was 1.8 +/- 0.8. These findings demonstrate that U74006F can significantly protect locomotor function in our model of compression spinal cord injury if administered as late as 4 hours postinjury. Delaying administration of the compound to 8 hours after injury results in considerable loss of its protective capabilities even if the dose is increased threefold.

Novel 21-aminosteroids that inhibit iron-dependent lipid peroxidation and protect against central nervous system trauma.

A novel class of 21-aminosteroids has been developed. Compounds within this series are potent inhibitors of iron-dependent lipid peroxidation in rat brain homogenates with IC50's as low as 3 microM. Furthermore, selected members enhance early neurological recovery and survival in a mouse head injury model. Significant improvement in the 1 h post-head-injury neurological status (grip test score) by as much as 168.6% of the control has been observed. The most efficacious compound in this assay (30) showed an increase in the 1-week survival of 78.6% as compared to 27.3% for the vehicle-treated mice in the head-injury model. Based on its biological profile, 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16 alpha- methylpregna-1,4,9(11)-triene-3,20-dione monomethanesulfonate (30) was selected for further evaluation and is currently entering phase I clinical trials for the treatment of head and spinal trauma.

Effects of a 21-aminosteroid (U-74006F) on cerebral metabolites and edema after severe experimental head trauma.

U-74006F, a 21-aminosteroid, is a potent inhibitor of CNS tissue LP in vitro. In this study it was tested for effects on brain edema and metabolites after impact injury to the closed skull. Anesthetized cats were blindly treated with U-74006F or vehicle at 30 min (1 mg/kg) and 2.5 hr (0.5 mg/kg) after head or sham injury. They were sacrificed 4 hr after injury by in situ fixation of the brain. Head-injured cats were selected for unilateral (left) cerebral contusion. Metabolites (enzyme fluorometry) and edema (specific gravity) were measured in the cerebral cortex and white matter bilaterally. Cerebral hemisphere, contusion, and vasogenic edema volumes were morphometrically measured. Magnitude of edema and metabolites in tissue with vasogenic edema was similar in vehicle- and drug-treated cats. By contrast, the cortex and nonedematous white matter neighboring contusion in drug-treated cats had lactate, glucose, and glycogen levels that suggested an improved metabolic state over vehicle treatment. Most metabolites were not affected by trauma or treatment in the uncontused hemisphere. These results suggest that postinjury treatment with the nonglucocorticoid steroid U-74006F may benefit the metabolism of nonedematous tissue adjacent to contusion.