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PubMed2005

Repeated injections of 131I-rituximab show patient-specific stable biodistribution and tissue kinetics.

PURPOSE: It is generally assumed that the biodistribution and pharmacokinetics of radiolabelled antibodies remain similar between dosimetric and therapeutic injections in radioimmunotherapy. However, circulation half-lives of unlabelled rituximab have been reported to increase progressively after the weekly injections of standard therapy doses. The aim of this study was to evaluate the evolution of the pharmacokinetics of repeated 131I-rituximab injections during treatment with unlabelled rituximab in patients with non-Hodgkin's lymphoma (NHL). METHODS: Patients received standard weekly therapy with rituximab (375 mg/m2) for 4 weeks and a fifth injection at 7 or 8 weeks. Each patient had three additional injections of 185 MBq 131I-rituximab in either treatment weeks 1, 3 and 7 (two patients) or weeks 2, 4 and 8 (two patients). The 12 radiolabelled antibody injections were followed by three whole-body (WB) scintigraphic studies during 1 week and blood sampling on the same occasions. Additional WB scans were performed after 2 and 4 weeks post 131I-rituximab injection prior to the second and third injections, respectively. RESULTS: A single exponential radioactivity decrease for WB, liver, spleen, kidneys and heart was observed. Biodistribution and half-lives were patient specific, and without significant change after the second or third injection compared with the first one. Blood T(1/2)beta, calculated from the sequential blood samples and fitted to a bi-exponential curve, was similar to the T(1/2) of heart and liver but shorter than that of WB and kidneys. Effective radiation dose calculated from attenuation-corrected WB scans and blood using Mirdose3.1 was 0.53+0.05 mSv/MBq (range 0.48-0.59 mSv/MBq). Radiation dose was highest for spleen and kidneys, followed by heart and liver. CONCLUSION: These results show that the biodistribution and tissue kinetics of 131I-rituximab, while specific to each patient, remained constant during unlabelled antibody therapy. RIT radiation doses can therefore be reliably extrapolated from a preceding dosimetry study.

Antibodies, Monoclonal↗
PubMed2005

O-(2-[18F]fluoroethyl)-L-tyrosine PET for monitoring the effects of convection-enhanced delivery of paclitaxel in patients with recurrent glioblastoma.

PURPOSE: Convection-enhanced delivery (CED) of paclitaxel is a new locoregional approach for patients with recurrent glioblastoma. The aim of this study was to evaluate O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) in monitoring the effects of this type of direct drug delivery. METHODS: Eight patients with recurrent glioblastoma underwent CED of paclitaxel, which was infused over stereotactically placed catheters into the tumour. FET PET and MRI were performed before and 4 weeks after therapy and then at 3-month intervals to document follow-up. For quantitative evaluation, SUV(max)(tumour)/SUV(mean)(background) ratios were calculated. RESULTS: At baseline all tumours showed gadolinium enhancement and high FET uptake (SUV(max)/BG 3.2+/-0.8). Four weeks after CED, a statistically significant decrease in FET uptake was seen (SUV(max)/BG-17%; p<0.01). During follow-up, no recurrence was observed within the CED area. Two out of eight patients with extended tumours died 4 and 5 months after treatment, most probably from local complications. Temporarily stable disease with stable FET uptake was observed in six of eight patients; this was followed by progression and increasing FET uptake ratios (+46%) distant from the CED area in five of the six patients 3-13 months after CED. One patient still presents stable FET uptake 10 months after CED. MRI showed unchanged/increasing contrast enhancement and oedema without ability to reliably assess disease progression. CONCLUSION: FET PET is a valuable tool in monitoring the effects of CED of paclitaxel. In long-term follow-up, stable or decreasing FET uptake, even in contrast-enhancing lesions, is suggestive of reactive changes, whereas increasing ratios appear always to be indicative of recurrence. Therefore, FET PET is more reliable than MRI in differentiating stable disease from tumour regrowth.

Antineoplastic Agents↗
PubMed2006

Local infusion of norepinephrine reduces blood losses and need of transfusion in total knee arthroplasty.

Blood loss after total knee arthroplasty (TKA) is often associated with cardiovascular complications and a high transfusion rate of allogenic blood. In our study we focused our attention on developing a new intra-surgical procedure that appears safe, easy to perform and effective in the reduction of bleeding in TKA. We evaluated 84 patients who underwent TKA and met our inclusion criteria; they were assigned to two groups: 55 controls in which a saline solution was used to wash the surgical field before tourniquet release, and a second group of 29 patients, in which a saline solution containing a low dose of norepinephrine was locally applied before tourniquet release. The local administration of a low dose of norepinephrine has induced a significant reduction of perioperative blood loss and blood transfusion requirements; in addition, this method was characterised by the absence of complications or adverse effects. In conclusion, our data suggest that intraoperative local administration of a low dose of norepinephrine could represent an effective and safe method of reducing blood loss and preventing blood transfusions in patients with TKA.

Aged↗
PubMedDate not supplied

Radiofrequency thermal ablation: increase in lesion diameter with continuous acetic acid infusion.

PURPOSE: To evaluate the influence of continuous infusion of acetic acid 50% during radiofrequency ablation (RFA) on the size of the thermal lesion produced. METHODS: Radiofrequency (RF) was applied to excised bovine liver by using an expandable needle electrode with 10 retractable tines (LeVeen Needle Electrode, RadioTherapeutics, Sunnyvale, CA) connected to a commercially available RF generator (RF 2000, RadioTherapeutics, Sunnyvale, CA). Experiments were performed using three different treatment modalities: RF only (n = 15), RF with continuous saline 0.9% infusion (n = 15), and RF with continuous acetic acid 50% infusion (n = 15). RF duration, power output, tissue impedance, and time to a rapid rise in impedance were recorded. The ablated lesions were evaluated both macroscopically and histologically. RESULTS: The ablated lesions appeared as spherical or ellipsoid, well-demarcated pale areas with a surrounding brown rim with both RF only and RF plus saline 0.9% infusion. In contrast, thermolesions generated with RF in combination with acetic acid 50% infusion were irregular in shape and the central portion was jelly-like. Mean diameter of the coagulation necrosis was 22.3 +/- 2.1 mm (RF only), 29.2 +/- 4.8 mm (RF + saline 0.9%) and 30.7 +/- 5.7 mm (RF + acetic acid 50%), with a significant increase in the RF plus saline 0.9% and RF plus acetic acid 50% groups compared with RF alone. Time to a rapid rise in impedance was significantly prolonged in the RF plus saline 0.9% and RF plus acetic acid 50% groups compared with RF alone. CONCLUSIONS: A combination of RF plus acetic acid 50% infusion is able to generate larger thermolesions than RF only or RF combined with saline 0.9% infusion.

Acetic Acid↗
PubMedDate not supplied

Radiofrequency ablation with a new perfused-cooled electrode using a single pump: an experimental study in ex vivo bovine liver.

The purpose of this study was to assess the efficacy of a new perfused-cooled electrode that uses a single pump for creating a large ablation zone in explanted bovine liver. This was done by comparing with the radiofrequency (RF) ablation zones that were created with a monopolar cooled electrode to the RF ablation zones that were created by the new perfused-cooled electrode. We developed a new perfused-cooled electrode that uses a single pump by modifying a 17-gauge cooled electrode (Radionics) with a 2.5-cm outer metallic sheath (15-gauge) in order to allow use of the internal cooling water (5.85 % hypertonic saline) for the infused saline. Thirty ablation zones were created in explanted bovine livers (12-min ablation cycle; pulsed technique; 2000 mA, maximum) with three different regimens: group A, RF ablation with the 17-gauge cooled electrode; group B, RF ablation with the 15-gauge cooled electrode; group C, RF ablation with the perfused-cooled electrode. T2-weighted magnetic resonance (MR) imaging was obtained immediately after RF ablation for calculating volumes of the ablation zone. Following MR imaging, the ablation zones were excised and measured for transverse diameters and vertical diameters. The transverse diameter, vertical diameter, and the calculated volumes of the ablation zones on MR imaging were compared among the groups. Ablation zones created with the perfused-cooled electrode (group C) were significantly larger than those created with the 17-gauge cooled electrode (group A) and the 15-gauge cooled electrode (group B) according to the transverse diameter and vertical diameter on the gross specimens (p < 0.05): 3.6 +/- 0.38 cm and 4.4 +/- 0.20 cm in group A, 3.7 +/- 0.08 cm and 4.6 +/- 0.16 cm in group B, and 5.4 +/- 0.65 cm and 6.0 +/- 0.56 cm in group C, respectively. On the MR imaging, the calculated volumes of the ablation zones in group C were significantly larger than those in groups A and B (p < 0.05): 23.1 +/- 8.7 cm3 in group A, 28.9 +/- 5.7 cm3 in group B, and 80.0 +/- 34 cm3 in group C, respectively. A new perfused-cooled electrode using a single pump could efficiently increase the size of the ablation zone in liver compared with a monopolar cooled electrode, and this was due to its simultaneous use of internal cooling and saline infusion.

Analysis of Variance↗
PubMed2002

Treatment of tendopathies with tropisetron.

A comparison between a local anesthetic drug and the 5-hydroxytryptamine 3 (5-HT3) receptor antagonist tropisetron in treating tendopathies or periarthropathies revealed that tropisetron has a longer effect on resting pain and pain on movement than the local anesthetic drug. The most likely explanation for this effect probably is a blocking of stimulated 5-HT3 receptors at the nociceptors in conjunction with an inhibited release of substance P and other neurokines because of this blockage. Further studies will have to show whether the action of tropisetron in tendopathies is as favorable as that of corticosteroids.

Anesthetics, Local↗
PubMed2002

Treatment of chronic wounds by local delivery of granulocyte-macrophage colony-stimulating factor in patients with neutrophil dysfunction.

Chronic wounds are associated with considerable morbidity and prolonged hospitalizations. The availability of recombinant growth factors and cytokines provides a new modality for treatment of recalcitrant wounds. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a growth protein for hematopietic cells, also enhances neutrophil and monocyte function and promotes keratinocyte proliferation. In three patients with inherited disorders associated with leukocyte dysfunction and non-healing wounds, topical application of GM-CSF resulted in complete wound closure within 1 to 4 weeks. A subcutaneous (s.c.) infusion pump for the local s.c. delivery of GM-CSF was also found to enhance healing. Local application of GM-CSF may thus promote wound closure in patients with impaired wound healing.

Administration, Topical↗
PubMed2006

Effect of catheter-based transendocardial delivery of stromal cell-derived factor 1alpha on left ventricular function and perfusion in a porcine model of myocardial infarction.

BACKGROUND: Myocardial regeneration after myocardial infarction can occur via stem cell recruitment. Stromal cell-derived factor 1alpha (SDF-1alpha) has been shown to be critical for stem cell homing to injured tissue. METHODS: Myocardial infarction was induced in pigs via microembolization of the distal left anterior descending artery. Two weeks after myocardial infarction animals underwent catheter-based transendocardial injection of SDF-1alpha into the periinfarct myocardium (18 injections, 5 ìg per injection) (n = 12) or sham-intervention (n = 8). Tc99m sestamibi single-photon emission computed tomography (SPECT) and electromechanical mapping (EMM) of the left ventricle were performed two and seven weeks after myocardial infarction. RESULTS: Infarct size by tetrazolium staining was similar in both groups (8.9 +/-1.2% of left ventricle vs. 8.9 +/- 2.6%). Vessel density in the periinfarct area was significantly higher in SDF-1alpha treated animals than in controls (349 +/- 17/mm2 vs. 276 +/- 21/mm2, p < 0.05). Myocardial perfusion (SPECT) did not change in either group. Ejection fraction and stroke volume (EMM) decreased in SDF-1alpha animals and increased in controls (difference between groups p = 0.05 for ejection fraction and p < 0.05 for stroke volume). Linear local shortening (EMM) did not change in controls (11.4 +/- 1.3% to 11.5 +/- 0.5%) but decreased significantly in SDF-1alpha treated animals (12.1 +/- 0.9% to 8.4 +/- 0.9%, p < 0.05, p < 0.05 for difference between groups). SDF-1 delivery was associated with a substantial loss of collagen in the periinfarct area (32+/-5% vs. 61+/-6% in control animals, p < 0.005). CONCLUSION: A strategy to augment stem cell homing by catheter-based transendocardial delivery of SDF-1alpha in experimental myocardial infarction increases periinfarct vessel density, fails to improve myocardial perfusion, is associated with loss of collagen in the periinfarct area and impairs left ventricular function.

Animals↗
PubMed2002

The effect of intraoperative bupivacaine administration on parenteral narcotic use after laparoscopic appendectomy.

BACKGROUND: Little is known about the effect that prophylactic administration of local anesthesia into surgical incisions has on pain and analgesic use after laparoscopic appendectomy. We examined how preemptive infiltration of a local anesthetic affected the use of parenteral narcotics after laparoscopic appendectomy. METHODS: We conducted a retrospective chart review of 60 patients who underwent a laparoscopic appendectomy from January 2000 to April 2001 at our institution. We studied the association between prophylactic bupivacaine analgesia and patterns of postoperative parenteral narcotic use. RESULTS: Of 46 patients who received intraoperative bupivacaine, 24 (52%) required postoperative parenteral narcotics as compared with 12 (86%) of 14 patients who did not receive bupivacaine (risk difference, 34%; 95% confidence interval [CI], 10-51%; p = 0.02). After adjustment for other factors, the patients who received prophylactic bupivacaine were much less likely to receive parenteral narcotics during their postoperative hospital stay than the patients who did not receive prophylactic bupivacaine (odds ratio, 0.2; 95% CI, 0.1-0.9; p = 0.03). Furthermore, the patients who received prophylactic bupivacaine required fewer doses (median number of doses, 0.5; interquartile range [IQR], 0-2) of parenteral narcotics postoperatively than those who did not receive bupivacaine (median, 2; IQR, 1-4; p value for comparison, 0.03). CONCLUSION: Intraoperative bupivacaine infiltrated locally into surgical wounds is associated with both a decreased need for postoperative parenteral narcotics and a reduced number of doses in patients who have undergone a laparoscopic appendectomy.

Adult↗
PubMed2006

The use of ciliary neurotrophic factor to promote recovery after peripheral nerve injury by delivering it at the site of the cell body.

Despite a body of evidence showing that various neurotrophic factors support the survival of nerve cells and stimulate axonal outgrowth, doubt remains about their optimal site of application as well as the more compelling question of what clinical benefit, if any, they would confer. Ciliary neurotrophic factor (CNTF) supports the survival of motorneurons in vitro and in vivo. Direct delivery of CNTF to the cell bodies may help reduce the side effects and overcome the problem of rapid systemic clearance. The aim of this study was to establish whether nerve regeneration may be improved upon by the controlled addition of a specific humoral neurotrophic substance (CNTF) at the level of the cell body. Three groups of five adult sheep were used. The first group acted as normal controls. In the second and third groups, the median nerve was divided and repaired using an epineurial suture technique. In the second group, CNTF was supplied into the CSF at the level of C6 by an implanted osmotic pump. In the third group physiological saline was placed in the osmotic pump. The animals underwent comprehensive electrophysiological and isometric tension experiments at six months. All of the animals had reduced electrophysiological, morphometric and isometric tension indices after surgery compared to normal. The CNTF group had better results than the saline group in the following; (1) area and amplitude of the muscle action potential (2) the percentage of tetanus and muscle mass preserved after repair. These differences were only statistically significant for amplitude of the muscle action potential. No statistical difference was found in the morphological indices (fibre diameter, axon diameter, myelin thickness and internodal length) between the CNTF and saline groups. CNTF does not confer a functional benefit when applied at the level of the cell body.

Animals↗
PubMed2005

Intratumoral delivery of mitoxantrone in association with 90-Y radioimmunotherapy (RIT) in recurrent glioblastoma.

Twenty-six recurrent Glioblastoma (rGBM) patients sequentially treated at the National Neurological Institute 'C Besta' were enrolled for a second surgery in order to remove recurrent tumor and to place an Ommaya reservoire to allow local delivery of chemotherapy and local pre-targeted radio-immunotherapy (RIT). All patients had partial tumor resection and 75% of them had a residual tumor mass after exeresis larger than 2 cm. After surgery all patients were managed with a second line systemic chemotherapy (PCV). Moreover the protocol scheduled two cycles of local RIT (90 Yttrium 5- 25 mCi per cycle) with a 10 week interval. Locoregional mitoxantrone chemotherapy was locally delivered as a single dose of 4 mg every 20 days. Responses to treatment were assessed by monthly neurological examination and by MRI or contrast-enhanced CT scan performed every 2 months. For the whole group of patients the PFS after second surgery at 6 and 12 months was 61% and 22%, respectively and survival after recurrence at 6, 12 and 18 months was 80%, 53% and 42%, respectively. Neither major side effects occurred systemically nor related on the place of local injections. The percentage of long-term survivors was very high: 42% of patients were still alive at 18 months. We stress the concept that the combined treatments could be more effective if delivered into a smaller residual tumor mass and probably in an adjuvant setting, before tumour recurrence.

Adolescent↗
PubMed2006

Lactacystin exhibits potent anti-tumor activity in an animal model of malignant glioma when administered via controlled-release polymers.

Lactacystin, a proteasome-inhibitor, has been shown to induce apoptosis of experimental gliomas in vitro. However, its systemic toxicity prevents further clinical use. To circumvent this problem, lactacystin can be delivered intratumorally. We tested the efficacy of lactacystin incorporated into controlled-release polymers for treating experimental gliomas. 9L-gliosarcoma and F98-glioma cell lines were treated with lactacystin (10-100 microg/ml) for 72 h in vitro. Cell-viability was measured with MTT-assays. Toxicity of lactacystin/polycarboxyphenoxypropane-sebacic-acid (pCPP : SA) polymers was tested in vivo using Fischer-344 rats intracranially implanted with lactacystin polymers loaded from 0.1 to 2% lactacystin by weight. The efficacy of 1, 1.3, 1.5 and 1.7% lactacystin/pCPP : SA polymers was determined in Fischer-344 rats intracranially challenged with 9L and treated either simultaneously or 5 days after tumor implantation. Lactacystin was cytotoxic in 9L cells, causing a 16 +/- 8% growth inhibition at 10-microg/ml that increased to 78 +/- 4% at 100-microg/ml. Similarly, lactacystin inhibited growth of F98 by 18 +/- 8% at 10-microg/ml and 74 +/- 2% at 100-microg/ml in vitro. Polymers released lactacystin for 21 days and intracranial implantation in rats neither generate local nor systemic toxicity at doses lower than 2%. Treatment with lactacystin/pCPP : SA polymers with loading concentrations of 1.0, 1.3, and 1.5% prolonged survival of animals intracranially challenged with 9L when polymers where inserted in the day of tumor implantation. In conclusion, lactacystin exhibits potent cytotoxic-activity against 9L and F98 in vitro, it can be efficiently incorporated and delivered using controlled-release polymers, and at the proposed concentrations lactacystin polymers are safe for CNS delivery and prolong survival in the 9L model.

Acetylcysteine↗
PubMed2006

Metabolic manipulation of glioblastoma in vivo by retrograde microdialysis of L-2, 4 diaminobutyric acid (DAB).

OBJECTIVES: To study the metabolic effects in vivo of L-2, 4 diaminobutyric acid (DAB) administered by retrograde microdialysis in glioblastoma and to evaluate the feasibility of the technique. METHODS: In 10 patients with glioblastoma, a stereotactic biopsy was performed followed by implantation of microdialysis catheters. One or two catheters were implanted in tumor tissue and two reference catheters were implanted in normal brain tissue and subcutaneous abdominal tissue, respectively. Tumor catheters were perfused with 80 or 120 mmol/l DAB and reference catheters were perfused with a Ringer solution, all with a flow rate of 2.0 microl/min. Treatment was given for at mean 9.1 (5-19) days. RESULTS: The treatment was well tolerated by the patients with the exception of two patients in whom a transient brain edema appeared. No complications related to the technique were encountered. During treatment, an increase in the extracellular amino acids alanine, glycine, glutamate, aspartate, serine, threonine, and taurine was found demonstrating a significant influence on the intracellular pool of free amino acids induced by DAB. No change in glucose metabolism or glycerol was evident. The metabolism in normal brain was unaffected during treatment. CONCLUSIONS: Retrograde microdialysis is a feasible method for intracerebral administration of drugs to tumor tissue in patients with glioblastoma. We found it possible to deliver DAB to glioblastoma tumors in fully mobilized patients and to assess the metabolic effects induced by the treatment. The changes in extracellular amino acids were in concordance to what was expected from in vitro studies. Elevation of glutamate and taurine may be regarded as markers for an induced cellular toxicity while the unchanged level of glycerol may indicate no direct effects on phospholipase activity and membrane phospholipid composition. The effects were restricted to the tumor compartment. Although an improved survival could possibly be suspected no dramatic effect on outcome could be detected. However, the series was small and, most probably, the time for treatment was too short.

Aged↗
PubMed2006

Local intracerebral administration of O(6)-benzylguanine combined with systemic chemotherapy with temozolomide of a patient suffering from a recurrent glioblastoma.

The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is a major determinant of methylating anticancer drug resistance. Inactivation of MGMT by pseudosubstrate inhibitors, such as O(6)-benzylguanine (O(6)BG), sensitizes tumor cells to O(6)-alkylating agents. However, systemic administration of O(6)BG causes depletion of MGMT in all tissues of the body. Therefore, dose reduction of O(6)-alkylating drugs administered together with O(6)BG is required in order to avoid unwished toxic side effects. To attenuate the increased systemic toxicity caused by MGMT inhibitors, local MGMT inactivation would be desirable. Here, we report on intracerebral treatment with O(6)BG of a patient suffering from glioblastoma. O(6)BG was administered weekly in the tumor cavity by means of an Ommaya reservoir. This application was well tolerated. Concomitant treatment with temozolomide (Temodal) was associated with transient tumor stabilization without detectable side effects. Although evidence is still lacking that local O(6)BG administration caused MGMT to be depleted in the residual tumor, the trial shows that intracerebral treatment with O(6)BG is feasible. It might be a safe strategy for improving glioma therapy by treatment with temozolomide (and presumably also other O(6)-alkylating drugs) concomitant with O(6)BG without augmenting drug-induced systemic side effects.

Adult↗
PubMedDate not supplied

Therapeutic effect of lipoprostaglandin E1 on sudden hearing loss.

PURPOSE: The authors conducted a prospective, comparative clinical trial for the purpose of additional effect of lipoprostaglandin E 1 (lipo-PGE 1 ) on sudden hearing loss. MATERIALS AND METHODS: With the approval of the institute ethics committee, a total of 128 consecutive patients with diagnoses of sudden hearing loss were included in the study. The patients in the lipo-PGE 1 group received continuous infusion of 10 microL lipo-PGE 1 and 48 mg methylprednisolone for 5 days, and the patient in the control group were treated with only 48 mg methylprednisolone. RESULTS: The total recovery rate after the treatment was 67.2%. There were 70.5% recovery rate in lipo-PGE 1 group and 60.5% recovery rate in control group. However, no significant differences were observed in the improvements of pure tone average and subjective symptoms between the lipo-PGE 1 and control groups. CONCLUSION: The results failed to prove a beneficial effect of lipo-PGE 1 in the treatment of sudden hearing loss in spite of its higher cure rate.

Alprostadil↗
PubMed2005

Docosahexaenoic acid-induced amelioration on impairment of memory learning in amyloid beta-infused rats relates to the decreases of amyloid beta and cholesterol levels in detergent-insoluble membrane fractions.

We investigated the effects of dietary administration of docosahexaenoic acid (DHA; C22:6n-3) on the levels of amyloid beta (A beta) peptide (1-40) and cholesterol in the nonionic detergent Triton 100 x-insoluble membrane fractions (DIFs) of the cerebral cortex and, also, on learning-related memory in an animal model of Alzheimer's disease (AD) rats infused with A beta peptide (1-40) into the cerebral ventricle. The infusion increased the levels of A beta peptide and cholesterol in the DIFs concurrently with a significant increase in reference memory errors (measured by eight-arm radial-maze tasks) compared with those of vehicle rats. Conversely, the dietary administration of DHA to AD-model rats decreased the levels of A beta peptide and cholesterol in the DIFs, with the decrease being more prominent in the DHA-administered rats. Regression analysis revealed a significant positive correlation between A beta peptide and each of cholesterol, palmitic acid and stearic acid, and between the number of reference memory errors and each of cholesterol, palmitic, stearic and oleic acid; moreover, a significant negative correlation was observed between the number of reference memory errors and the molar ratio of DHA to palmitic plus stearic acid. These results suggest that DHA-induced protection of memory deficits in AD-model rats is related to the interactions of cholesterol, palmitic acid or stearic acid with A beta peptides in DIFs where DHA ameliorates these interactions.

Alzheimer Disease↗
PubMed2004

Synchronous extraperitoneal and intraperitoneal dissemination of appendix cancer.

BACKGROUND: The aim of this study was to report the role of combined treatments, including cytoreductive surgery and perioperative regional chemotherapy, in patients with synchronous systemic and intraperitoneal dissemination of appendix cancer. METHODS: Patients with synchronous systemic and intraperitoneal dissemination of appendix cancer were treated with cytoreductive surgery and perioperative regional chemotherapy. Variables statistically analyzed with survival as an end point included demographic characteristics, prior surgical score (PSS), tumour marker levels, peritoneal cancer index (PCI), and completeness of cytoreduction (CC). RESULTS: Mean follow up was 42.6 months, median survival time (MST) for 15 patients was 28 months and 5-year survival rate was 29.4%. Female patients had a longer MST than male patients (p=0.0199). Survival was better in patients with PSS 0 and 1 (p=0.0277). Patients with elevated CEA and CA 19-9 levels had a shorter MST (p=0.0083 and p=0.0193, respectively). PCI and CC comparisons did not show significant differences. Morbidity (n=2) and mortality (n=2) rates were 13.3% respectively. CONCLUSION: Acceptable morbidity and mortality and a 29.4% 5-year survival rate allows cytoreductive surgery and regional chemotherapy to be considered as a treatment option for selected patients with synchronous systemic and intraperitoneal dissemination of appendix cancer.

Adenocarcinoma, Mucinous↗
PubMed2006

Cavitary pyoderma gangrenosum treated with local infusion of corticosteroid.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare inflammatory skin condition, characterized by progressive and recurrent skin ulceration, often representing a pathergy response. OBSERVATIONS: We report a case of spontaneous retrosternal PG that developed on the background of previous PG of the skin of the back. The patient had underlying ulcerative colitis. After failure of prednisone, minocycline, and dapsone, a novel method was instituted. Local flushing with dexamethasone, by a radiologically inserted retrosternal catheter with precordial suction, induced a rapid and sustained response. Subsequently maxillary sinus PG developed after the patient's tooth extraction. This responded to local corticosteroid injections in combination with systemic corticosteroid. LIMITATIONS: Further reports of this technique are required to consolidate its use and infusion variables. CONCLUSIONS: Two unusual sites of PG have been described, with successful treatment by a novel local steroid infusion. The profound sensitivity to trauma is demonstrated, which suggests that prophylactic corticosteroid may be useful for essential surgical intervention.

Biopsy, Needle↗