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In ischemic stroke, selectively cooling the ischemic penumbra might lead to neuroprotection while avoiding systemic complications. Because penumbral tissue has reduced cerebral blood flow and in vivo brain temperature measurement remains challenging, the effect of different methods of therapeutic hypothermia on penumbral temperature are unknown. We used the COMSOL Multiphysics® software to model a range of cases of therapeutic hypothermia in ischemic stroke. Four ischemic stroke models were developed with ischemic core and/or penumbra volumes between 33–300 mL. Four experiments were performed on each model, including no cooling, and intraarterial, intravenous, and active conductive head cooling. The steady-state temperature of the non-ischemic brain, ischemic penumbra, and ischemic core without cooling was 37.3 °C, 37.5–37.8 °C, and 38.9–39.4 °C respectively. Intraarterial, intravenous and active conductive head cooling reduced non-ischemic brain temperature by 4.3 °C, 2.1 °C, and 0.7–0.8 °C respectively. Intraarterial, intravenous and head cooling reduced the temperature of the ischemic penumbra by 3.9–4.3 °C, 1.9–2.1 °C, and 1.2–3.4 °C respectively. Active conductive head cooling was the only method to selectively reduce penumbral temperature. Clinical studies that measure brain temperature in ischemic stroke patients undergoing therapeutic hypothermia are required to validate these hypothesis-generating findings. [ABSTRACT FROM AUTHOR]

Graft versus host disease (GVHD) is one of the most serious complications following stem cell transplant in children and is a major cause of morbidity and mortality. Corticosteroids remain the mainstay of treatment, and although a majority of children respond to systemic steroids, those refractory to or dependent upon corticosteroids suffer from complications secondary to long-term steroid administration. This problem has prompted consideration of steroid-sparing treatment strategies, although the time to clinical remission can be variable. Intraarterial corticosteroid delivery has been used in adults as a rescue therapy in steroid-resistant patients, but its use in children has been limited. We investigated the feasibility of intraarterial steroid administration into the bowel and/or liver in a cohort of six pediatric patients with acute GVHD. All patients successfully underwent treatment with no serious adverse effects. Five of five (100%) patients with gastrointestinal bleeding due to GVHD had rapid symptom improvement by 48 h, which was durable up to three weeks. Three of four (75%) patients with hepatic GVHD had improved cholestasis following intraarterial steroid administration. Our experience with this small cohort preliminarily demonstrated the feasibility and safety of intraarterial steroid administration in children with acute GVHD. This approach warrants consideration as a rescue therapy in steroid-refractory cases and as a "bridge" therapy for children with severe acute GVHD who are transitioning to steroid-sparing regimens. [ABSTRACT FROM AUTHOR]

Aim: Stroke results in long term serious disability that affect millions across the globe. Several clinical and preclinical studies have reinforced the therapeutic use of stem cells in stroke patients to enhance their quality of life. Previous studies from our lab have demonstrated that 1*105 allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) when given intraarterially (IA) render neuroprotection by modulating the expression of inflammasomes. Sirtuins are a class of important deacylases having a significant role in cellular functioning. Sirtuin-1 (SIRT-1) is an important enzyme essential for regulating cellular metabolism, which is reduced following an ischemic episode. The present study aims to unviel the role of MSCs in regulating the brain SIRT-1 levels following stroke and the involvement of SIRT-1 in regulating inflammasome signaling to reduce cellular apoptosis towards rendering neuroprotection. Materials and Methods: 6 h post-reversible middle cerebral artery occlusion (MCAo), ovariectomized Sprague Dawley (SD) rats were infused intraarterially with 1*105 MSCs. 24 h after MCAo animals were examined for functional and behavioral outcomes. Brains were collected for assessing size of infarct and neuronal morphology. Molecular and immunofluroscence studies were also performed for assessing changes in gene and protein expressions. Extent of apoptosis was also determined in different groups. Inhibition study with SIRT-1 specific inhibitor EX-527 was also performed. Results: A reduction in infarct size and improvement in motor functional and behavioral outcomes following infusion of MSCs IA at 6 h post-stroke was observed. Increase in average neuronal density and neuronal length was also seen. Increased expression of SIRT-1, BDNF and concomitant reduction in the expression of different inflammatory and apoptotic markers in the brain cortical regions were observed following MSCs treatment. Conclusion: Our study provides a preliminary evidence that post-stroke IA MSCs therapy regulates SIRT-1 to modulate NF-κB pathway to mitigate inflammasome signaling and cellular apoptosis. This study using IA approach for administering MSCs is highly relevant clinically. Our study is the first to report that neuroprotective effects of IA MSCs in rodent focal ischemia is mediated by SIRT-1 regulation of inflammasome signaling. [ABSTRACT FROM AUTHOR]

Purpose: A systematic review to determine the effectiveness of intra-arterial anaesthetics on post- operative pain and opioid analgesia requirements in arterial embolisation procedures. Materials and methods: A systematic review of the literature was performed (Embase, PubMed, MEDLINE and the Cochrane Library) from inception to 10th August 2020. Randomised controlled trials (RCTs) and cohort studies that utilised intra-arterial anaesthesia during an embolisation procedure for the purposes of pain control were included. Eligibility was assessed by two investigators independently. Results: Eight hundred fifty-nine candidate articles were identified, and 9 studies met the inclusion criteria (6 RCTs and 3 retrospective cohort studies). Four studies were of hepatic chemoembolisation and 5 were of uterine artery embolisation. Five hundred twenty-nine patients were treated in total. All studies used lidocaine as the anaesthetic with doses ranging from 20 to 200 mg, and the anaesthetic was delivered varyingly before, during or after embolisation. Pain intensity was converted to a numeric scale from 0 to 10, and opioid doses were converted to milligram morphine equivalent doses. A random-effects meta-analysis model was used to analyse the results of RCTs, and the results of cohort studies were summarised with a narrative synthesis. The meta-analyses suggested that pain scores were reduced by a mean of 1.02 (95% CI − 2.34 to 0.30; p = 0.13) and opioid doses were reduced by a mean of 7.35 mg (95% CI, − 14.77, 0.06; p = 0.05) in the intervention group however neither finding was statistically significant. No serious adverse events were reported. Conclusion: Intra-arterial anaesthetic may slightly reduce pain intensity and post-operative opioid consumption following embolisation, however the results are not statistically significant. There is very limited data available on the effect of anaesthetic on length of hospital admission. Whilst no serious adverse events were reported, there are some concerns regarding the effect of lidocaine on the technical success of embolisation procedures that preclude our recommendation for routine use in embolisation procedures. High quality randomised controlled trials are required to elucidate the dose-response effect of lidocaine on opioid consumption and pain following embolisation, particularly in the first few hours post-operatively, as well as effects on duration of hospital stay. [ABSTRACT FROM AUTHOR]

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Copyright of Journal of the Society of Thoracic Carido-Vascular Anaesthesia & Intensive Care is the property of Gogus Kalp Damar Anestezi ve Yogun Bakim Dernegi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article presents the case study of a 54-year-old man with a rare case of intravascular schwannoma, the most common peripheral nerve tumors in adults. These tumors are typically found on flexor extremities, head and neck and mediastinum. The patient was presented to the hospital with a painful, skin-colored nodule on the posterior neck.

Background: Osteosarcoma is the most common primary malignancy of bone. Its treatment relies on the administration of neoadjuvant and adjuvant chemotherapy combined with surgery. Alternative to common intravenous (i.v.) administration of chemotherapeutic drugs, clinical studies also evaluated the benefit of intraarterial (i.a.) administrations. However, conflicting results were obtained when both routes of administration of cisplatin (CDDP), a gold standard drug in osteosarcoma treatment, were compared. In order to overcome clinical confounding factors, we evaluated both routes of drug administration in a mouse model of experimental osteosarcoma. Methods: We directly compared i.v. versus i.a. drug infusions of cisplatin (CDDP), in an orthotopic xenograft mouse model of metastatic osteosarcoma. We performed tumor monitoring using caliper and micro computed tomography and measured tumor perfusion using laser speckle contrast imaging. Histopathological changes were evaluated using hematoxylin and eosin staining as well as immunohistochemistry (cleaved PARP-1, CD31, HIF-1α). Results: First, an effective concentration of 4 mg/kg i.a. CDDP was determined that significantly reduced primary tumor volume. We used this concentration of i.a. CDDP and compared it to infusions of i.v. CDDP. Systemic (i.v.) CDDP only showed minor suppression of tumor growth whereas local (i.a.) CDDP strongly inhibited tumor growth and destruction of cortical bone in the tumor-bearing hind limb. Inhibition of tumor growth was linked to a reduced blood perfusion and resulted in increased amounts of tumor necrosis after i.a. CDDP. After treatment with i.a. CDDP, remaining viable tumor tissue responded by increasing expression of HIF-1a. Side effects due to administration of CDDP were minor, showing no differences in kidney damage between i.v. and i.a. CDDP. However, increased epidermal apoptosis in the foot was an indirect marker for locally increased concentrations of CDDP. Conclusions: Our findings demonstrate the great potential of local administration of cytotoxic chemotherapeutics, such as CDDP. Consequently, we provide a preclinical basis for a renewed interest in the clinical use of i.a. chemotherapy in osteosarcoma therapy. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab (BV) has been used to treat recurrent glioblastoma with a progression free survival of approximately 3-3.5 months. Typically, it is administered intravenously every 2-3 weeks at dosages ranging from 5-15 mg/kg. Serious side effects include Gl tract perforations, hematologic disorders, intracranial hemorrhage, and malignant hypertension. We hypothesized that selective intracranial intra-arterial infusion (SIACI) of BV following blood/brain barrier disruption (BBBD) with mannitol may allow for reduced dosage, lower toxicity, and equivalent or superior progression free survival (PFS). Methods: Sixteen patients (8 males & 8 females) with a mean age of 55 years (range 27-68), KPS>70, and recurrent glioblastoma were enrolled. All patients underwent super-selective catheterization and were given a single intra-arterial dose of 15 mg/kg BV following osmotic blood/brain barrier disruption with mannitol to the arteries supplying the tumor. The patients had no additional treatment following that initial SIACI mannitol and BV until they met criteria for progression. PFS was assessed using modified Response Assessment in Neuro-Oncology (RANO) criteria. Results: Median progression free survival from only one dose of SIACI mannitol and BV was 3.9 months. Side effects included seizure in 2 patients, and headache in 1 patient. Seizures were well controlled with medications, and there were no serious toxicities. There were no endovascular-related complications. Conclusion: SIACI of mannitol and BV at 15mg/kg allows for similar or better PFS compared to biweekly treatments of IV BV at 10mg/kg. The dosage required is lower and side effects were minimal and well tolerated. Future larger trials are warranted to assess whether repeated less frequent IA mannitol and BV may be superior to biweekly IV administration as a monotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the frequency and the predictive factor of each feeding artery on intra-arterial infusion chemotherapy (IAIC) in primary tongue cancer.Materials and Methods: We retrospectively evaluated 20 patients who received IAIC for primary tongue cancer. The main and accompanying feeding arteries were identified on super-selective angiography of the branches of the external carotid artery. Tumor diameter, and extension to the contralateral side, tongue extrinsic muscles (TEMs), and lateral mesopharyngeal wall were determined based on magnetic resonance imaging or computed tomography findings.Results: The main feeding artery was the ipsilateral lingual artery (LA) in 15 of the 20 examined tumors and the contralateral LA in the other 5. Ten cancers had only one feeding artery, and multiple feeding arteries were detected in the remaining 10. Tumors >4 cm (n = 9), those with extension to the contralateral side (n = 13), and those with extension to TEMs (n = 15) were supplied by significantly larger numbers of feeding arteries compared to tumors without these features (P = 0.01, 0.049, and 0.02, respectively). The frequency of feeding from the contralateral LA was 64 % (9/14) and 17 % (1/6) in tumors with and without extension to the contralateral side, respectively. Feeding from a facial artery (FA) was not detected in tumors ≤4 cm, while 5 of the 9 (56 %) tumors >4 cm were supplied by a FA (P = 0.01).Conclusion: A careful search for feeding arteries is required, especially in large tumors with extension to the contralateral side or to TEMs. [ABSTRACT FROM AUTHOR]

Copyright of Revista Academica Ciencia Animal is the property of Revista Academica Ciencia Animal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Intraarterial (IA) drug delivery is a physiologically appealing strategy as drugs are widely distributed throughout the tumor capillary network and high regional tissue concentrations can be achieved with low total doses. IA treatment of glioblastoma multiforme (GBM) has been attempted since the 1950s but success has been elusive. Although IA treatments have been embraced for the treatment of retinoblastoma and advanced liver cancers, this has not been the case for GBM. The development of IA drug delivery for the treatment of brain cancer over the last several decades reveals a number of critical oversights. For example, very few studies took into consideration the underlying hydrodynamic factors. Therapeutic failures were often blamed on an inability to penetrate the blood brain barrier or on the streaming of drugs. Similarly, there were few methods to investigate the ultra-fast pharmacokinetics of IA drugs. Despite past failures, clinical interest in IA drugs for the treatment of GBM persists. The advent of modern imaging methods along with a better understanding of hydrodynamics factors, better appreciation of the complex morphology of GBM, improved drug selection and formulations, and development of methods to minimize treatment-related neurological injury, promise to considerably advance the application of IA drugs for GBM treatment. There are several clinical trials with IA treatments in the National Trial Registry that are actively recruiting patients. This review of IA drug delivery for GBM treatment is therefore timely and is intended to assess how this method of drug delivery could be better applied to future treatments. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to evaluate the safety and effectiveness of transcatheter arterial embolization (TAE) for stopping bleeding following hip surgery. Methods: We performed a 12-year retrospective analysis of 13 patients (M:F = 6:7, median age 72 years) who underwent angiography for bleeding following hip surgery. The types of surgery, latency time, angiographic findings, TAE details, procedure-related complications, and clinical outcomes were analyzed. Technical success was defined as no further bleeding detected on angiography following embolization. Results: Total hip replacement arthroplasty was the most common surgery performed for these patients ( n = 10). Seven of the 13 study patients underwent angiography the same day as their surgery. Angiograms showed active ( n = 11) or suspicious ( n = 1) bleeding in 12 of the 13 patients. Gelatin sponge particles, coils, NBCA, PVA, and their combinations were used as the embolic material. For the one patient without obvious signs of bleeding, prophylactic TAE was done to achieve bleeding control. For the 11 patients with active bleeding, 10 underwent technically successful TAE, and 1 patient underwent surgery due to a large pseudoaneurysm located near the bifurcation of the common femoral artery. There were no major procedure-related complications or patient mortality. The 30-day mortality rate was 15 % (2/13), and both of these patients died of multiorgan failure. Conclusions: Transcatheter angiography is useful for identifying bleeding arteries. TAE is safe and effective for managing bleeding after hip surgery. [ABSTRACT FROM AUTHOR]

Rapid first pass uptake of drugs is necessary to increase tissue deposition after intraarterial (IA) injection. Here we tested whether brain tissue deposition of a nanoparticulate liposomal carrier could be enhanced by coordinated manipulation of liposome surface charge and physiological parameters, such as IA injection during transient cerebral hypoperfusion (TCH). Different degrees of blood-brain barrier disruption were induced by focused ultrasound in three sets of Sprague-Dawley rats. Brain tissue retention was then compared for anionic, cationic, and charge-neutral liposomes after IA injection combined with TCH. The liposomes contained a non-exchangeable carbocyanine membrane optical label that could be quantified using diffuse reflectance spectroscopy (DRS) or visualized by multispectral imaging. Real-time concentration-time curves in brain were obtained after each liposomal injection. Having observed greater tissue retention of cationic liposomes compared to other liposomes in all three groups, we tested uptake of cationic liposomes in C6 tumor bearing rats. DRS and multispectral imaging of postmortem sections revealed increased liposomal uptake by the C6 brain tumor as compared to non-tumor contralateral hemisphere. We conclude that regional deposition of liposomes can be enhanced without BBB disruption using IA injection of cationic liposomal formulations in healthy and C6 tumor bearing rats. [ABSTRACT FROM AUTHOR]

Over the past 20 years, clinical research has focused on the development of reperfusion therapies for acute ischemic stroke (AIS), which include the use of systemic intravenous thrombolytics (alteplase, desmoteplase, or tenecteplase), the augmentation of systemic intravenous recanalization with ultrasound, the bridging of intravenous with intra-arterial thrombolysis, the use of multi-modal approaches to reperfusion including thrombectomy and thromboaspiration with different available retrievers. Clinical trials testing these acute reperfusion therapies provided novel insight regarding the comparative safety and efficacy, but also raised new questions and further uncertainty on the field. Intravenous alteplase (tPA) remains the fastest and easiest way to initiate acute stroke reperfusion treatment, and should continue to be the first-line treatment for patients with AIS within 4.5 h from onset. The use of tenecteplase instead of tPA and the augmentation of systemic thrombolysis with ultrasound are both novel therapeutical modalities that may emerge as significant options in AIS treatment. Endovascular treatments for AIS are rapidly evolving due to technological advances in catheter-based interventions and are currently emphasizing speed in order to result in timely restoration of perfusion of still-salvageable, infarcted brain tissue, since delayed recanalization of proximal intracranial occlusions has not been associated with improved clinical outcomes. Comprehensive imaging protocols in AIS may enable better patient selection for endovascular interventions and for testing multi-modal combinatory strategies. [ABSTRACT FROM AUTHOR]

Transient cerebral hypoperfusion (TCH) has empirically been used to assist intraarterial (IA) drug delivery to brain tumors. Transient (<3 min) reduction of cerebral blood flow (CBF) occurs during many neuro- and cardiovascular interventions and has recently been used to better target IA drugs to brain tumors. In the present experiments, we assessed whether the effectiveness of IA delivery of cationic liposomes could be improved by TCH. Cationic liposomes composed of 1:1 DOTAP:PC (dioleoyl-trimethylammonium-propane:phosphatidylcholine) were administered to three groups of Sprague-Dawley rats. In the first group, we tested the effect of blood flow reduction on IA delivery of cationic liposomes. In the second group, we compared TCH-assisted IA liposomal delivery versus intravenous (IV) administration of the same dose. In the third group, we assessed retention of cationic liposomes in brain 4 h after TCH assisted delivery. The liposomes contained a near infrared dye, DilC(7), whose concentration could be measured in vivo by diffuse reflectance spectroscopy. IA injections of cationic liposomes during TCH increased their delivery approximately fourfold compared to injections during normal blood flow. Optical pharmacokinetic measurements revealed that relative to IV injections, IA injection of cationic liposomes during TCH produced tissue concentrations that were 100-fold greater. The cationic liposomes were retained in the brain tissue 4 h after a single IA injection. There was no gross impairment of neurological functions in surviving animals. Transient reduction in CBF significantly increased IA delivery of cationic liposomes in the brain. High concentrations of liposomes could be delivered to brain tissue after IA injections with concurrent TCH while none could be detected after IV injection. IA-TCH injections were well tolerated and cationic liposomes were retained for at least 4 h after IA administration. These results should encourage development of cationic liposomal formulations of chemotherapeutic drugs and their IA delivery during TCH. [ABSTRACT FROM AUTHOR]

We treated a patient with biopsy-proven, chemotherapy-resistant testicular cancer liver metastasis using Y-90 selective internal radiation treatment. We chose yttrium-90 rather than surgery and ablation due to tumor location and size as well as the patient's clinical history. The result was marked tumor response by positron emission tomography and computed tomography as well as significant improvement of the patient's quality of life accompanied by a substantial decrease of his tumor markers. [ABSTRACT FROM AUTHOR]

The novel ability to quantify drug and tracer concentrations in vivo by optical means leads to the possibility of detecting and quantifying blood brain barrier (BBB) disruption in real-time by monitoring concentrations of chromophores such as Evan's Blue. In this study, experiments were conducted to assess the disruption of the BBB, by intraarterial injection of mannitol, in New Zealand white rabbits. Surgical preparation included: tracheotomy for mechanical ventilation, femoral and selective internal carotid artery (ICA) catheterizations, skull screws for monitoring electrocerebral activity, bilateral placement of laser Doppler probes and a small craniotomy for the placement of a fiber optic probe to determine tissue Evan's Blue dye concentrations. Evans Blue (6.5 mg/kg) was injected intravenously (IV) just before BBB disruption with intracarotid mannitol (25%, 8 ml/40 s). Brain tissue concentrations of the dye in mannitol-treated and control animals were monitored using the method of optical pharmacokinetics (OP) during the subsequent 60 min. Hemodynamic parameters, heart rate, blood pressure, and EKG remained stable throughout the experiments in both the control and the mannitol-treated group. Brain tissue concentrations of Evan's Blue and the brain:plasma Evan's Blue partition coefficient progressively increased during the period of observation. A wide variation in brain tissue Evan's Blue concentrations was observed in the mannitol group. The experiments demonstrate the feasibility of measuring tissue concentrations of Evan's Blue without invading the brain parenchyma, and in real-time. The data suggest that there are significant variations in the degree and duration of BBB disruption induced with intraarterial mannitol. The ability to optically monitor the BBB disruption in real-time could provide a feedback control for hypertonic disruption and/or facilitate dosage control for chemotherapeutic drugs that require such disruption. [ABSTRACT FROM AUTHOR]

Thrombolytic stroke therapy is based on the "re-canalization hypothesis," i.e., that reopening of occluded vessels improves clinical outcome in acute ischemic stroke through regional reperfusion and salvage of threatened tissues. Re-canalization is an important predictor of stroke outcome in all the modalities of thrombolysis. Thrombolysis in acute ischemic stroke evolved from clinical trials with intravenous (IV) tissue plasminogen activator (tPA) to combination treatments with Intra-arterial (IA)/mechanical reperfusion techniques. The combined approach reduces time to initiation of treatment and may increase re-canalization and chances of a good clinical outcome. In IV thrombolysis overall re-canalization rate is 46.2% during the first 6-24 hrs. Intra-arterial thrombolysis has higher early re-canalization rate, 63.2%. The highest re-canalization rate is seen with mechanical thrombolysis, 83.6%. Other factors in addition to re-canalization: stroke severity, older age, systolic hypertension, location of arterial occlusion, collateral blood supply, and time from stroke onset to treatment play an important role in determining the clinical outcome following thrombolysis with tPA. Future trials should look at the interplay of various factors like re-canalization, reperfusion, and collateral flow and clot burden in the evaluation of reperfusion therapies in acute ischemic stroke. [ABSTRACT FROM AUTHOR]

A debate is emerging over whether the treatment time window in acute stroke can be extended beyond 6 h if penumbral tissue can be identified. Treatment decisions are very difficult in cases of tandem proximal carotid occlusion with arterioarterial intracranial embolism. We enter this debate with the present report on a case of atherosclerotic proximal carotid occlusion and resulting periocclusional carotid T embolism that was successfully treated 9 h after symptom onset. The case of a 68-year-old man with fluctuating symptoms of right-hemispheric stroke is presented (NIHSS score 12–20 on admission). CT angiography demonstrated proximal carotid occlusion and periocclusional embolism of the entire internal carotid artery (ICA) including the carotid T segment. Penumbral tissue was diagnosed by nonenhanced and perfusion CT imaging 7.5 h after symptom onset. Treatment was initiated 9 h after symptom onset by passing the proximal occlusion with a microcatheter and local administration of recombinant tissue plasminogen activator (rt-PA) into the carotid T segment at the level of posterior communicating artery (PCoA) origin. Recanalization of the ICA and middle cerebral artery was accomplished within 1 h by flow establishment via the PCoA. The atherosclerotic proximal ICA occlusion was not stented due to the risk of embolism from remnant thrombi in the petrous and cavernous ICA segments. Follow-up MRI showed only mild haemorrhagic infarct transformation of the initial infarct core. The patient was discharged from hospital 18 days after treatment with NIHSS score 5. If penumbral tissue can be conclusively identified, endovascular treatment in proximal and intracranial tandem occlusion can be successful, even in treatments initiated 6–9 h after stroke onset. If the intracranial flow after recanalization can be established via the circle of Willis, the underlying proximal ICA occlusion may not require treatment. [ABSTRACT FROM AUTHOR]

Summary: Purposes: We report our experience with sodium methohexital (Brevital) as an anesthetic used in the Wada test for language and memory in 86 epilepsy surgery patients (173 procedures). Methods: The methods are compared with those of the more commonly used anesthetic sodium amobarbital (Amytal). Results: Despite differences between the methohexital and amobarbital test protocols, the behavioral and neurologic effects of the two anesthetics are similar. Because of the brief duration of methohexital, two successive injections are made on each side rather than one, to lengthen the time available for testing both language and memory. Behavioral and EEG indices return to baseline more quickly and more completely with methohexital than with amobarbital, allowing several repetitions of the procedure without incremental drowsiness, and the total time taken for the procedure is less with methohexital than with amobarbital. Conclusions: The results of language and memory testing in the Wada test are equivalent for amobarbital and methohexital, except that methohexital has a briefer duration of action and is associated with less sedation. [ABSTRACT FROM AUTHOR]

Precis: Intraarterial delivery of 50 mg/m² cisplatinum on a monthly basis is a welltolerated regimen for patients with nonresectable hepatoma. The selective uptake of cisplatinum delivered intraarterially suggests other selective intraarterial protocols would be of use in regional cancers treated with cisplatinum. Background: Sixty-seven patients with nonresectable hepatoma were treated with hepatic artery infusions (HA1) of 50 mg/m² cisplatinum on a monthly basis. Methods: Forty-eight patients received an initial course of whole liver external radiation with intravenous (IV) cisplatinum 50 mg/m². Nineteen patients did not receive radiation and received HAI cisplatinum only. All patients then received HAI cisplatinum at 50 mg/m² on a monthly basis. Six patients were given a tracer dose of radioactive [sup 195m]cisplatinum for quantitation by the HAI and IV routes. Results: Monthly HAI cisplatinum was well tolerated and could be repeated indefinitely. Median survival for primarily treated nonresectable hepatomas was 12 months [alpha fetoprotein (AFP) elevated] and 17.5 months (AFP negative). Radioactive cisplatinum given by HAI yielded 34-55% tumor uptake of cisplatinum vs. < 5% by IV delivery. Conclusions: Hepatic intraarterial cisplatinum at 50 mg/m² is a well-tolerated monthly regimen for patients with nonresectable hepatoma. [ABSTRACT FROM AUTHOR]

The plasma pharmacokinetics of adriamycin and 4′epi-adriamycin were studied in patients with malignant tumors of the liver after simultaneous regional administration of equal amounts of the two anthracyclines by the arterial route. The use of a highly selective liquid chromatographic analytical method permitted quantification of plasma concentrations of the two drugs as well as their corresponding 13-hydroxy metabolites. The plasma concentrations of each drug followed a three-compartment open model. On average the area under the plasma concentration time curve (AUC) and the maximum plasma concentration ( C ) were 2.1 and 1.7 times larger for adriamycin than for 4′epi-adriamycin, respectively. 4′Epi-adriamycin was eliminated faster than adriamycin, the terminal half-life time being on the average 1.5 times higher for adriamycin. These findings are in agreement with what has previously been observed after intravenous administration. The plasma concentrations of the 13-hydroxy metabolites did not exceed 30 ng ml. The AUC values of these metabolites were on average 20% of the AUC values of the intact drugs. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of adriamycin in patients with malignant tumours of the liver were studied after peripheral intravenous treatment and after regional administration of the drug either by the arterial route or by the portal vein, with or without hepatic artery ligation. The plasma concentration of adriamycin after intravenous as well as after intrahepatic administration followed a three-compartment open model. The results in the present study confirm previous reports of a large inter-individual variation of the pharmacokinetics of adriamycin. After intravenous administration the individual variations in AUC/mg/m and C /mg/m (dose normalized area under plasma concentration time curve and dose normalized maximum plasma concentration, respectively) were more than 5-fold. The area under the plasma concentration time curve (AUC) was on the average 1.5 times higher after the peripheral intravenous administration than after intrahepatic administration. The reduction of maximum plasma concentration ( C ) of adriamycin after intrahepatic administration was even more pronounced than the reduction in AUC (mean value C iv/ C ihep=1.7). The plasma concentration of adriamycinol did not exceed 20 ng/ml. The AUC values of adriamycinol were 20% (median value) of the AUC values of adriamycin, indicating the importance of adriamycinol in the adriamycin therapy. [ABSTRACT FROM AUTHOR]

A 56 year old man presented with increasing abdominal pain. He suffered from arterial occlusive disease with occlusion of the right A. iliaca communis. Angiography revealed partial thrombotic occlusion of the superior mesenteric artery. Urokinase (UK) at a dose of 150 IU/kg × minutes and heparin (1,000 U/h) was infused through the 7F angiographic catheter for 180 minutes. After 70 min of treatment, angiography showed improvement, and after 120 min the thrombus was nearly completely lysed. A stenosis of approximately 50% was still present after 180 min. Two hours after treatment the patient was pain free without analgesics. laboratory studies showed systemic fibrinogenolysis, but fibrinogen was still within the upper normal range. Only slight systemic fibrinolytic activity (<5 IU UK/ml) could be determined. However, α-antiplasmin was depleted. The catheter was drawn 15 h after thrombolysis without bleeding. While under concurrent heparin and phenprocoumon therapy, the patient developed an infected gluteal hematoma as a result of i.m. injections prior to this treatment. A repeat angiography approximately one month after thrombolysis revealed further improvement and patency. The patient is well and free of abdominal angina and under oral anticoagulant therapy. [ABSTRACT FROM AUTHOR]

Sixteen patients with intracerebral tumors received intraarterial cisplatin, teniposide, and BCNU combined with intravenous cisplatin, teniposide, and cytosine arabinoside. Oral glycerol and intravenous mannitol were given along with the intravenous chemotherapy in an attempt to increase drug delivery to tumor by augmenting tumor blood flow. Thirteen additional patients were treated with the same regimen, but received all the chemotherapy intravenously. Of the 16 patients receiving intraarterial chemotherapy (median survival, 14 weeks), none responded, 5 (31%) were stable for > 8 weeks, 8 (50%) failed, and 3 (19%) were unevaluable due to early death. Of the 13 patients receiving all their treatment intravenously (median survival, 13 weeks), 3 (23%) responded, 1 (8%) was stable, 7 (54%) failed, and 2 (15%) were unevaluable due to early death. In the patients receiving intraarterial chemotherapy, toxicity included ipsilateral retinal toxicity (2 patients), ocular pain or headache (10), periorbital swelling and flushing (6), increased brain edema with focal neurological deficits and drowsiness (5), and catheter-related carotid artery thrombosis followed by fatal herniation (1). Myelosuppression was worse in patients who received all their treatment intravenously than in those receiving intraarterial chemotherapy (p < 0.05). Neutropenic sepsis developed in 4 patients on the intraarterial arm (1 fatal) and in 5 patients on the intravenous arm (2 fatal). Other toxic effects were similar whether or not patients received intraarterial treatment or only intravenous treatment. Overall, toxicity of this regimen was excessive, and response rates were lower than would have been expected with single agent therapy. [ABSTRACT FROM AUTHOR]

A prospective, controlled and standardized animal experiment was performed to study the influence of various anticancer drugs. The Novikoff hepatoma transplanted into male Spraque-Dawley rats was treated with fluorouracil (FUra), mitomycin C, methotrexate, cisplatin and fluorodeoxyuridine (FdUrd) at equi-effective dosage, in terms of side effects (weight loss), in comparison to a control group (0.9% saline solution) by locoregional application via the hepatic artery. The tumor multiplication factor (TMF = tumor volume day 12/tumor volume day 5) served as the parameter to compare the tumor growth of the various groups. All drugs showed a significant ( P<0.05) effect on the tumor growth. In comparison to the control group (mean TMF 9.66), FdUrd (3.78) and FUra (3.03) only limited the tumor growth, mitomycin C (0.96) produced stable tumor, cisplatin (0.64) and methotrexate (0.15) significantly reduced ( P<0.01) the tumor size. We suggest that, in addition to the established (FUra, FdUrd, mitomycin C) drugs, methotrexate and cisplatin should be considered in further studies of the treatment of primary and secondary liver malignancies. [ABSTRACT FROM AUTHOR]

The effect of continuous and discontinuous locoregional chemotherapy with Floxuridine (FUdR) was studied in a standardized and controlled animal model, using the transplantable Novikoff hepatoma in Sprague-Dawley rats. The liver was perfused after transplantation with a total of 420 mg/kg FUdR, via a fully implanted osmotic minipump or miniport and catheter in the hepatic artery, either continuously ( n=22) from day 5 to day 12, or discontinuously ( n=28) on days 5 and 8. Viable tumor volume and peritumorous cell infiltration were measured. No reduction in tumor volume was attained using discontinuous therapy, in contrast to a highly significant reduction using continuous therapy ( P<0.001). Significantly less cell infiltration was found after discontinuous than after continuous therapy. In conclusion, continuous locoregional chemotherapy with FUdR was the superior administration method on measurable tumor effect, when compared to discontinuous infusion. [ABSTRACT FROM AUTHOR]

Purpose. To perform an intra-arterial dose escalation studyof carboplatin based on hemispheric blood-flow estimation inpatients with recurrent malignant glioma. The primary purposewas to determine the maximally tolerated intra-arterial dose.Methods and patients. Methods included: 1) selective intra-arterialdelivery performed with modern microcatheters, 2) pulsatile infusion,and 3) dosage based on local cerebral blood-flowestimation (middle cerebral artery 60%, anterior cerebral artery20%, posterior cerebral artery 15%, and anterior choroidalartery 5% of the hemispheric blood-flow). The deliverieswere performed above the ophthalmic artery in theanterior circulation, or above the anterior inferior cerebellararteries in the posterior circulation. The doses wereescalated from 200 mg/hemisphere at 50 mg increments.Twenty-one patients were studied (14 with glioblastoma multiforme,five anaplastic astrocytoma, one aggressive low-grade glioma, onemetastasis). Patients had recurrent glioma limited to onehemisphere and Karnofsky score of 50 or greater.Concomitant therapies were allowed. Results. Carboplatin was escalatedto a dose of 1400 mg/hemisphere. One patienthad a permanent neuromotor decline. The predominant toxicitywas hematopoietic. The median time to tumor progressionwas 22 weeks, median survival 39 weeks, andthe response rate 70% (50% SD and 20%PR) of 19 patients. Conclusions. Hemispheric blood-flow estimationallowed us to escalate the dose of intra-arterialcarboplatin to twice what was previously considered safe.Responses compared favorably to previous studies. Further studiesare needed to determine if this method willprovide improved and durable responses. [ABSTRACT FROM AUTHOR]

Normal New Zealand White rabbits were used to compare theoretical brain concentrations (based upon pharmacokinetic modeling) with actual experimental concentrations of BCNU following intraarterial (IA) or intravenous (IV) infusions. IA infusion therapy for brain tumor patients has been promising based upon theoretical predictions but of limited effectiveness clinically. Experimentally-measured rabbit carotid artery flow rates (63.9 ± 3.4 ml/min) [mean ± 1 sem] and BCNU systemic clearances (197 ± 10.2 ml/min) predicted a theoretical IA advantage of 4.1 ± 0.2. lpsilateral brain concentrations of BCNU during and after IA infusions (20 mg/min/m over 15 minutes) were: 16.2 ± 2.9, 19.0 ± 3.9, 20.3 ± 2.8, 4.8 ± 2.5, 2.1 ± 1.5, and 1.7 ± 1.6 μg/gm brain at 5, 10, 15, 25, 35, and 45 minutes after infusion start. Mean concentrations at same time points in contralateral hemisphere (IA infusions) were: 7.1 ± 1.8, 9.0 ± 1.8, 10.3 ± 0.7, 4.2 ± 1.4, 2.2 ± 1.2, 2.0 ± 1.5 μg/gm brain. Concentrations in either hemisphere during IV infusions were similar to contralateral hemisphere during IA infusions. Comparison of ipsilateral: contralateral hemisphere ratios during and after IA infusions were: 3.2 ± 0.4, 2.6 ± 0.3, 2.2 ± 0.3, 1.1 ± 0.3, 1.0 ± 0.4, and 0.9 ± 0.3 at the same time points. Although these data show higher drug concentrations with IA infusions, actual values were considerably less than predicted by theoretical modeling. This discrepancy between theoretical and experimental results emphasizes need for further study of causes and remedies so that IA therapy can achieve better drug concentrations with less toxicity. [ABSTRACT FROM AUTHOR]

Animal studies suggest that hyperglycaemia directly affects local blood flow and vascular reactivity. We studied the effects of 7 h of local forearm hyperglycaemia, on forearm (muscle) and skin microcirculatory blood flow in 12 healthy men. Furthermore, the effects of this local hyperglycaemia on forearm vasoreactivity to noradrenaline were studied. Using the perfused forearm technique, a local hyperglycaemia of approximately 16 mmol/l was induced by continuous intraarterial infusion of 5% glucose. All subjects received both glucose and placebo (0.9% NaCl) infusions on two different occasions, in random order and blinded for the subjects. Forearm (muscle) blood flow and vascular reactivity to noradrenaline were measured using venous occlusion plethysmography. Skin microcirculatory blood flow was evaluated using intravital capillary microscopy (nutritive blood flow) and laser-Doppler fluxmetry (thermoregulatory blood flow). Measurements were performed at baseline, after 4 h, and after 7 h of intraarterial glucose or placebo infusion. During local glucose infusion there was a slight increase in the levels of insulin, C-peptide, systemic glucose, and blood pressure, compared to the placebo experiments. No differences were observed in forearm blood flow and laser-Doppler flux ratio (infused: contralateral arm), as well as in capillary blood cell velocity between glucose and placebo experiments. Noradrenaline produced similar reductions in forearm blood flow ratio during glucose and placebo experiments. We conclude that in contrast to animal studies, local hyperglycaemia (≈ 16 mmol/1) for 7 h does not affect forearm macro and microcirculatory blood flow or vascular reactivity to noradrenaline in man. [ABSTRACT FROM AUTHOR]

The successful retrieval of a catheter fragment from the abdominal aorta by the wire snare technique, thus avoiding a major laparotomy, is reported. Whereas there are many published reports on the use of this technique in the venous circulation, similar experiences in the arterial circulation have been reported but rarely. [ABSTRACT FROM AUTHOR]