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At least 19 recordsLinked to original sources
PubMed1988

Intralesional infusion of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) for the treatment of patients with malignant brain tumor.

Twenty patients with supratentorial, intracerebral lesions defined by computed tomographic scan or magnetic resonance imaging were treated by surgery and adoptive immunotherapy with lymphokine-activated killer (LAK) cells and recombinant Interleukin-2 (rIL-2, Cetus). Seventeen patients had glioblastoma, two had high-grade oligodendroglioma, and one patient had two metastatic sarcoma lesions. LAK cells were produced from blood mononuclear cells (MNC) obtained by 2 to 3 leukapheresis procedures and cultured (2.5 x 10(6) MNC/ml) 3 to 5 days with 1000 units rIL-2/ml. Although LAK cells could be produced from MNC of all patients, those taking steroids or with a low Karnofsky functional status generated, on average, suboptimal LAK cell activity. Age, sex, and serum anticonvulsant levels do not seem to influence a patient's ability to produce LAK cells in vitro. For therapy, cultured MNC (1-15 x 10(9] containing LAK cells were suspended in saline containing 10(6) units rIL-2 and injected into tissue surrounding the tumor cavity during craniotomy. For 3 days after their operations, patients received 10(6) units rIL-2 into the tumor cavity through an Ommaya reservoir. The treatment protocol was tolerated well by all patients, although they all experienced some degree of headache, fever, or lethargy that cleared within a few days of the last rIL-2 injection. When computed tomographic (CT) scans were obtained soon after treatment, areas of low density suggested a greater-than-normal extent of edema around the operative site. At the present time, CT scans indicate that the tumors of seven patients have recurred with an average disease-free interval of 25 +/- 6 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

Efficacy of intralesionally administered cisplatin-impregnated biodegradable polymer for the treatment of 9L gliosarcoma in the rat.

OBJECTIVE: Use of biodegradable polymers for the local delivery of chemotherapy is a promising new strategy in the treatment of high-grade gliomas. We examine the benefit of local delivery of cisplatin, via biodegradable polymer, in the treatment of intracranial glioma in rats. This treatment is compared against intralesionally administered free cisplatin and systemic cisplatin. METHODS: The Fischer 344 9L gliosarcoma rat model was used with a cannula placed in the right frontal lobe. On Day 0, 5 x 10(3) 9L gliosarcoma cells were infused. Treatment was initiated on Day 7. In Experiment 1, polymer alone was infused intralesionally to rule out any inherent toxic or tumoricidal properties. In Experiment 2, polymer impregnated with 0.5, 5.0, and 25 mg/m2 cisplatin was infused intralesionally. In Experiment 3, the most effective dose of drug containing polymer was compared against a similar dose of intralesionally administered free cisplatin and the systemic administration of cisplatin. RESULTS: In Experiment 1, polymer alone demonstrated no inherent toxic or tumoricidal properties. In Experiment 2, polymer impregnated with 0.5 mg/m2 was 100% effective in eradicating intracranial tumor with minimal histological evidence of toxicity. At the 5.0 and 25 mg/m2 doses, local brain toxicity was significant. In Experiment 3, at Day 60, 8 of 12 animals treated with polymer containing 0.5 mg/m2 cisplatin were alive and tumor free. This compared with 3 of 13 tumor-free survivors for the group treated with intralesionally administered free cisplatin, and 0 of 13 and 0 of 11 survivors for the 50 and 100 mg/m2 intraperitoneally administered doses, respectively. CONCLUSION: The local instillation of cisplatin-impregnated biodegradable polymer, allowing the sustained release of high-dose chemotherapy locally, seems to be effective treatment for intracranial 9L gliosarcoma in the rat. Treatment was superior to intralesionally administered free or systemic cisplatin.

Animals↗
PubMed1991

Peptide T improves psoriasis when infused into lesions in nanogram amounts.

In each of 14 patients, two small but comparable psoriatic lesions were infused for 2 weeks with either saline or a saline solution of peptide T (as its analog D-ala1-peptide T amide) at 10(-7) mol/L with Alzet osmotic pumps worn extracorporeally. During infusion, lesions were photographed and scored for clinical features of psoriasis on a 9-point scale. After another 7 days, biopsy specimens were taken from the infused sites, and sections were scored for features of psoriasis on a 19-point scale. The differences between means for data from saline- and peptide T-infused lesions were evaluated statistically. Peptide T-infused lesions improved clinically; scores decreased from a mean of 4.35 initially to 1.57 at biopsy, whereas control lesions changed from 4.43 to 3.57 (p less than 0.01 for 1.57 vs 3.57). Histologic scores were also significantly different (5.28 for peptide T vs 10.00 for controls, 0.05 greater than p greater than 0.02). This study provides evidence that intralesionally infused peptide T demonstrates some clearing effect in psoriasis.

Adult↗
PubMed1997

Granulomatous cheilitis: a study of six cases.

OBJECTIVE: Granulomatous cheilitis (GC) is a very rare disorder of unknown etiology. Clinically, GC is characterised by recurrent swelling of the labial tissues, which may be followed by a permanent enlargement. Histologically, the typical form of GC is characterised by the formation of scattered aggregates of non-caseating granulomas. GC is the most frequent sign of orofacial granulomatosis, a disorder under which also encompasses sarcoidosis, Crohn's disease, atypical tuberculosis, Anderson-Fabry disease, possibly some allergic reactions, and Melkersson-Rosenthal syndrome (MRS). Some consider GC as an oligosymptomatic or monosymptomatic form of MRS. SUBJECTS AND METHODS: In this study we examined the clinical records of six patients presenting with GC which were examined and treated in the Department of Oral Medicine and Pathology of the Dental School of Aristotle University of Thessaloniki (Greece) during a 16-year period. In five of six patients a persistent swelling of the lower lip was recorded, one of whom also developed swelling in the upper lip. In one case the swelling was present in both lips and in another the GC was the only clinical finding, while in the other five cases it was accompanied by at least one other feature of MRS. In five cases, the histological picture revealed non-caseating granulomas. RESULTS: The treatment with the intralesional infusion of corticosteroids in three cases and the oral administration of corticosteroids in two cases was successful. One of the patients refused to be treated. This patient also presented later with permanent swelling of the upper lip.

Adult↗
PubMed2004

Pharmacological thrombolysis in Budd Chiari syndrome: a single centre experience and review of the literature.

BACKGROUND/AIMS: To review our experience of thrombolytic therapy in patients with acute Budd Chiari syndrome (BCS). METHODS: Records of 10 patients with BCS, treated by thrombolysis over a 12-year period were retrospectively analysed for demographics, clinical presentation/duration, primary disease, thrombolytic regimen, and follow-up. The same characteristics were also studied in previously reported patients. The agent used was recombinant tissue plasminogen activator (tPA) in all patients. RESULTS: Thrombolysis was used 12 times in 10 patients. Infusion was made systemically in three patients, into the hepatic artery in one patient, locally into a hepatic vein and/or IVC in four patients and locally within TIPS/portal vein in two patients. Only one infusion made systemically was partially successful. Adjunctive balloon angioplasty and/or stent insertion was undertaken for all eight procedures (in six patients) where local infusion was into the hepatic vein or TIPS. Six of these were ultimately successful (in five patients) and two were unsuccessful. Thrombolysis was more likely to be successful in the presence of a short history of thrombosis, when the thrombolytic agent was locally infused and when it was combined with a successful radiological procedure. Mean follow-up was 4.5 years (range 1-10 years). No serious bleeding complication occurred. CONCLUSIONS: We observed no benefit from thrombolysis when delivered systemically or arterially except in one case. Thrombolysis was useful in adjunctive management of BCS when the drug was infused locally into recently thrombosed veins that had appreciable flow following partial recanalisation. Thrombolysis was clearly of benefit in the repermeation of occluded/partially occluded hepatic veins/TIPS when early detection of new thrombus followed interventional procedures such as balloon angioplasty or stenting of hepatic veins.

Adolescent↗
PubMed2006

A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction.

AIMS: Mesenchymal stem cells (MSCs), rare bone marrow-derived stem cell precursors of non-haematopoietic tissues, have shown promise in potentially repairing infarcted myocardium. These and similar cell types are being tested clinically, but understanding of delivery and subsequent biodistribution is lacking. This study was designed to quantitatively compare MSC engraftment rates after intravenous (IV), intracoronary (IC), or endocardial (EC) delivery in a porcine myocardial infarction (MI) model. METHODS AND RESULTS: Allogeneic, male MSCs were cultured from porcine bone marrow aspirates. Iridium nanoparticles were added during culturing and internalized by the MSCs. An MI was induced in female swine (27-40 kg in size) by prolonged balloon occlusion of the mid-left anterior descending artery. Animals (n = 6 per group) were randomized to one of three delivery methods. Cellular engraftment was determined 14+/-3 days post-delivery by measuring ex-vivo the iridium nanoparticle concentration in the infarct. Confirmation of cellular engraftment utilized both DiI and fluorescence in situ hybridization (FISH) labelling techniques. During MSC infusion, no adverse events were noted. However, following IC infusion, half of the pigs exhibited decreased blood flow distal to the infusion site. At 14 days, the mean number of engrafted cells within the infarct zone was significantly greater (P< or =0.01) following IC infusion than either EC injection or IV infusion and EC engraftment was greater than IV engraftment (P< or =0.01). There was less systemic delivery to the lungs following [EC vs. IV (P = 0.02), EC vs. IC (P = 0.06)]. Both DiI and FISH labelling demonstrated the presence of engrafted male MSCs within the female infarcted tissue. CONCLUSION: IC and EC injection of MSCs post-MI resulted in increased engraftment within infarcted tissue when compared with IV infusion, and IC was more efficient than EC. However, IC delivery was also associated with a higher incidence of decreased coronary blood flow. EC delivery into acutely infarcted myocardial tissue was safe and well tolerated and was associated with decreased remote organ engraftment with compared with IC and IV deliveries.

Animals↗
PubMed2004

Intrapericardial delivery enhances cardiac effects of sotalol and atenolol.

Targeting drugs to the heart by intrapericardial (i.p.c.) delivery may be a promising strategy to obtain higher drug efficiencies with lesser side effects. We examined whether i.p.c. delivery of sotalol and atenolol in rats offers advantages over intravenous (i.v.) application. Following sustained IPC infusion of sotalol or atenolol, pericardial fluid levels exceeded plasma levels 97 and 134 times respectively (P < 0.01) resulting in 3.8 and 4.7 times higher overall left ventricular tissue drug levels (P < 0.05). In a second experiment, the effects of the i.p.c. or i.v. beta-blocker infusions on nitroprusside-induced tachycardia were studied in conscious rats. For both drugs, i.p.c. infusion of 0.03 mg/kg.h produced similar antitachycardiac effects as the 1 mg/kg.h i.v. dose. In a third set of studies, dP/dt max challenged by dobutamine infusion was assessed to study ventricular contractile function after i.v. and i.p.c. sotalol in anesthetized rats. i.p.c. sotalol infusion attenuated the dobutamine response curve to a greater extent than i.v. (P < 0.01). In conclusion, i.p.c. infusion of sotalol and atenolol results in high cardiac tissue concentrations with low systemic drug levels. Similar antitachycardiac effects can be obtained at a 10- to 30-fold lower dose compared with i.v. delivery. Also, depression of ventricular contractility is acquired at a substantially lower i.p.c. sotalol dose. Thus, beta-blocking properties of sotalol and atenolol can be greatly enhanced by applying them i.p.c.

Adrenergic beta-Antagonists↗
PubMed2003

Cytoreduction and intraperitoneal chemotherapy for the management of non-gynecological peritoneal surface malignancy.

Peritoneal surface malignancy can arise from pseudomyxoma peritonei, gastrointestinal carcinoma, abdomino-pelvic sarcoma and peritoneal mesothelioma. In the past, only palliative treatments were offered and the results were poor. We have proposed a new concept in managing patients with peritoneal surface malignancy. It involves an aggressive combined treatment modality of cytoreduction and perioperative intraperitoneal chemotherapy. The results are promising for patients with pseudomyxoma peritonei, peritoneal mesothelioma and well-selected patients with invasive peritoneal surface malignancies. The success in such comprehensive treatment depends on tumor biology, patient's co-morbidities, the completeness of cytoreduction, the efficacy of intraperitoneal chemotherapy administration and the surgeon's experience. The importance of patient selection is emphasized. The rationales and the outline of the current management strategies are described. Large phase II studies have demonstrated the marked survival advantage in this aggressive approach to peritoneal surface malignancy.

Antineoplastic Agents↗
PubMed2006

Postoperative analgesia after cesarean section by continued administration of levobupivacaine with the On-Q Painbuster system over the fascia vs ketorolac + morphine i.v.

OBJECTIVE: This study aimed to detect if continuous local infusion of levobupivacaine with the On-Q Painbuster system provided postoperative analgesia of similar quality to morphine + ketorolac i.v. in patients undergoing cesarean section. MATERIALS AND METHODS: Using a randomized prospective double-blind study, 20 women undergoing cesarean section with a standardized spinal technique were randomly assigned into two groups to receive either 10 mg morphine + 120 mg ketorolac + saline solution up to 96 ml with an elastomeric pump i.v. (group A) or local infusion of levobupivacaine 0.2% with the On-Q PAINBUSTER system (group B). Both groups were administered ketorolac i.v. in bolus in case of pain. RESULTS: The two groups differed in their VAS scores with group A experiencing significantly less pain than group B; the consumption of analgesics was significantly lower in group A than in group B. CONCLUSIONS: The i.v. system with morphine and ketorolac is more effective than levobupivacaine subcutaneous infusion in reducing postoperative pain associated with cesarean section.

Analgesics, Opioid↗
PubMed2004

Detection of 111In-oxine-labeled bone marrow stromal cells after intravenous or intralesional administration in chronic paraplegic rats.

Recent studies suggested that bone marrow stromal cells (BMSC) may have a therapeutic role in the treatment of paraplegia secondary to severe spinal cord injury (SCI). For this reason, we have studied the possibility of using nuclear medicine imaging techniques to evaluate the permanency and migration of BMSC after transplantation procedures in chronic paraplegic Wistar rats. After intravenous administration of 111In-oxine-labeled BMSC, gammagraphic images showed that the activity distributed all over the organism, but in the spinal cord only scarce activity was identified. When 111In-oxine-labeled BMSC were injected within the traumatic centromedullary cavity of paraplegic animals, the gammagraphic images showed persistent activity in the lesion zone, without any activity migrating to the rest of the organism, at least during the whole time of the study (10 days after transplantation procedures). Our results show the utility of 111In labeling for to know the permanency and distribution of BMSC after grafting procedures, and suggest the convenience of the intralesional administration of BMSC, instead of the intravenous administration, in the treatment of chronic traumatic paraplegia.

Animals↗
PubMed1994

Treatment with intralesional granulocyte instillations and interferon-gamma for a patient with chronic granulomatous disease and multiple hepatic abscesses.

We present the case of a 16-year-old girl with p22-deficient chronic granulomatous disease in whom multiple hepatic abscesses secondary to Staphylococcus aureus infection developed. Infection persisted despite extensive surgery and aggressive antibiotic therapy. Conventional intravenous granulocyte transfusions were not tolerated because of the development of alloantibodies to HLA. Treatment with interferon-gamma and intralesional granulocyte infusions was associated with dramatic clinical and radiographic improvement. No morbidity was associated with this therapy. To our knowledge, this is the first report of treatment with intralesional granulocyte instillations. Intralesional granulocyte instillation in association with interferon-gamma administration may result in clinical improvement in the conditions of patients with chronic granulomatous disease and hepatic abscesses for whom conventional therapy has failed.

Adolescent↗
PubMed2004

Long-term effects of carboplatin brainstem infusions on hearing thresholds in monkeys.

OBJECTIVE: To isolate the central auditory neurotoxicity of carboplatin from its well-established ototoxic effects. DESIGN: The "best-case scenario" of targeted drug delivery to brain cancer was simulated by infusing carboplatin directly into the brainstem of cynomolgus monkeys with chronically implanted catheters. Because this manner of drug administration produced low levels of carboplatin in spinal fluid and blood, it was assumed that resulting deficits were dictated by the central auditory neurotoxicity of platinum compounds and not peripheral ototoxic effects. The magnitude of this hearing loss was estimated by comparing the auditory brainstem response thresholds of treated monkeys with results from normal controls. SUBJECTS: Six adult male cynomolgus monkeys (Macaca fascicularis) weighing 4 to 6 kg (3 received carboplatin treatment and 3 served as normal controls). INTERVENTION: Brainstem infusions of carboplatin. RESULTS: The average threshold of carboplatin-treated monkeys was elevated 8.8 dB (SD = 7.3 dB) relative to normal controls 6 months after the termination of drug delivery and increased to 10.7 dB with less variation between subjects (SD = 5.6 dB) 1 year after drug treatment. Although small in magnitude, the hearing loss was statistically significant (P<.05). CONCLUSIONS: Brainstem infusions of carboplatin induced some degree of hearing impairment in all treated monkeys. These threshold elevations were modest compared with the ototoxic effects that have been reported after systemic doses of carboplatin. Our findings suggest that the neurotoxic sensitivity of cochlear hair cells is not shared by neurons in the central auditory pathways. As a result, methods for reducing the ototoxic effects of chemotherapy remain a viable strategy for preserving auditory function in patients with brain cancer.

Animals↗
PubMed2002

Intracoronary verapamil for reversal of no-reflow during coronary angioplasty for acute myocardial infarction.

No-reflow is a frequent observation during direct PTCA for acute myocardial infarction (AMI) and associated with a poor clinical outcome. This study assesses the value of verapamil for reversal of no-reflow during PTCA for AMI. In a consecutive series of 212 direct or rescue PTCAs for AMI, a TIMI flow grade < 3 was observed in 23 patients (10.8%). Ten of these patients had received GP IIb/IIIa antagonists before PTCA. Seven patients with AMI and TIMI grade 3 flow served as controls. All lesions were treated by stents. In 18 patients with systolic blood pressure > 90 mm Hg, nitroglycerine (0.1 mg i.c.) was given. Verapamil (1 mg over 2 min) was given via an infusion catheter distal to the angioplasty site. Before and after nitroglycerine, after verapamil, and 15 min later coronary flow was assessed by the TIMI frame count method (TFC). Nitroglycerine had no effect on TFC. Verapamil reduced TFC from 56 +/- 9 frames to 24 +/- 4 (P < 0.001). In controls, TFC did not change significantly. The TIMI flow grade was restored to TIMI flow grade 3 in 65%. In two of seven right coronary and one of three circumflex arteries, intermittent AV block II occurred during verapamil injection, which disappeared after atropine. No-reflow after PTCA for AMI can be reversed by intracoronary verapamil. This supports the hypothesis that no-reflow is caused by acute microvascular dysfunction probably because of a disorder in calcium homeostasis or microvascular spasm.

Aged↗
PubMed2003

Local convection enhanced delivery of IL4-Pseudomonas exotoxin (NBI-3001) for treatment of patients with recurrent malignant glioma.

PURPOSE: This was an open-label, dose-escalation trial of intratumoral administration of IL-4 Pseudomonas Exotoxin (NBI-3001) in patients with recurrent malignant glioma. PATIENTS AND METHODS: A total of 31 patients with histologically verified supratentorial grade 3 and 4 astrocytoma were studied. Of these, twenty-five patients were diagnosed with glioblastoma multiforme (GBM) while six were diagnosed with anaplastic astrocytoma (AA). Patients were over 18 years of age and had Karnofsky performance scores > or = 60. Patients were assigned to one of four dose groups in a dose-escalation fashion: 6 microg/ml x 40 ml, 9 microg/ml x 40 ml, 15 microg/ml x 40 ml, or 9 microg/ml x 100 ml of NBI-3001 administered intratumorally via stereotactically placed catheters. Patients were followed with serial MRI scans and clinical assessments every four weeks for the first 16 weeks and then every eight weeks until week 26. RESULTS: No drug-related systemic toxicity, as evident by lack of hematological or serum chemical changes, was apparent in any patients; treatment-related adverse effects were limited to the central nervous system. No deaths were attributable to treatment. Drug-related Grade 3 or 4 toxicity was seen in 39% of patients in all dose groups and 22% of patients at the maximum tolerated dose of 6 microg/ml x 40 ml. The overall median survival was 8.2 months with a median survival of 5.8 months for the GBM patients. Six-month survival was 52% and 48%, respectively. Gadolinium-enhanced magnetic resonance imaging of the brain showed areas of decreased signal intensity within the tumor consistent with tumor necrosis following treatment in many patients. CONCLUSIONS: NBI-3001 appears to have an acceptable safety and toxicity profile when administered intratumorally in patients with recurrent malignant glioma.

Adult↗
PubMed2003

Convection enhanced delivery of IL13-PE38QQR for treatment of recurrent malignant glioma: presentation of interim findings from ongoing phase 1 studies.

IL13PE38QQR is a recombinant toxin composed of the enzymatically-active portion of Pseudomonas Exotoxin A conjugated with human IL13. Binding of IL13-PE38 to the IL13 receptor (IL13R) permits internalization of the recombinant toxin resulting in selective and potent cytoxicity at nanomolar concentrations. Normal brain tissue expresses little or no IL13R, but malignant gliomas overexpress IL13R conferring the selective cytotoxicity to the agent. Convection-enhanced delivery (CED), a novel direct drug delivery method to tumor and peritumoral region uses positive pressure infusion to generate a pressure gradient that optimizes distribution of macromolecules within the brain. Three phase I studies have been initiated to investigate IL13-PE38QQR as an anti-tumor agent for the treatment of patients with recurrent malignant gliomas. As of January 2003 a total of 46 patients have been treated. The presentation at the March 2003 EANS Local Therapy of Glioma meeting reflects adverse event findings through January 2003 and survival data through March 2003. Intratumoral infusion with or without resection is fairly well-tolerated with corticosteroids prophylaxis particularly for patients with raised intracranial pressure. Post-resection infusion into the peritumoral brain parenchyma also appears to be very well tolerated. Histopathological tumor effect was seen at drug concentrations of 0.5-2.0 microg/mL. Although phase I studies do not focus on efficacy evaluation, prolonged survival times have been observed in this select population of patients. The preclinical data and details and preliminary results of the three clinical trials are reviewed.

Adult↗
PubMed2004

Application of molecular diagnosis for detection of peritoneal micrometastasis and evaluation of preoperative chemotherapy in advanced gastric carcinoma.

BACKGROUND: In advanced gastric cancer, peritoneal recurrence is the main cause of death after curative surgical resection. The aim of this report was to describe a novel approach for quantitative genetic diagnosis using peritoneal lavage for the identification of patients at high risk for peritoneal recurrence and for evaluation of the clinical response to intraperitoneal chemotherapy in advanced gastric cancer. METHODS: Nineteen patients with advanced gastric cancer who underwent staging laparoscopy and intraperitoneal chemotherapy before surgical resection or systemic chemotherapy between June 1999 and September 2001 were enrolled in this study. All peritoneal lavage specimens, collected at both staging laparoscopy and gastrectomy, were subjected to real-time quantitative genetic diagnosis. RESULTS: The reverse transcriptase polymerase chain reaction (RT-PCR) values decreased in 8 cases, stabilized as negative in 5, and increased in 6 during therapy. Patients whose RT-PCR values diminished and were ultimately negative survived except for one, and all but one patient whose values increased during treatment died of recurrence. CONCLUSIONS: Quantitative evaluation of genetic changes can provide accurate, useful information on the effects of preoperative intra-abdominal chemotherapy and overall prognosis for patients with advanced gastric cancer.

Adenocarcinoma↗
PubMed2005

Intra-articular volume assessment in glenohumeral instability.

It is commonly claimed that instability of the shoulder is associated with an enlarged joint volume. The purpose of our study was to assess the intra-articular volume in acute and chronic glenohumeral dislocation. Sixty-seven patients were examined by intra-articular infusion of saline solution. Three groups could be formed. Group 1 (n = 51) consisted of patients with first time traumatic dislocation, group 2 (n = 8) of cases with recurrent post-traumatic dislocation. The patients of group 3 (n = 8) suffered from impingement syndrome and served as the control group. The joint volume was correlated to the body surface area (BSA). We found a strong correlation between height, sex and intra-articular joint volume. There was no statistically significant difference in joint volume correlated to BSA between the three groups. There is no statistically significant difference in joint volume correlated to BSA in patients with traumatic anterior instability, chronic instability and individuals without glenohumeral instability.

Adolescent↗