Islet xenotransplantation: current status of preclinical studies in the pig-to-nonhuman primate model.

Purpose Of Review: Porcine islets are a major focus of current research in nonhuman primate xenotransplantation models. Major advances have been obtained recently and these are briefly described.

Recent Findings: Reports by three independent centres have described 6-month porcine islet xenograft survival in nonhuman primates.

Effects of long-term administration of high-dose recombinant human antithrombin in immunosuppressed primate recipients of porcine xenografts.

Background: Fibrin deposition is central to the acute humoral rejection process occurring in the presence of consumptive coagulopathy when pig organs are transplanted into primates.

Methods: To assess whether strategies aimed at preventing fibrin formation may extend xenograft survival, we administered high daily doses of recombinant human antithrombin (rhAT) (500 U/kg twice daily) to obtain both anticoagulant and anti-inflammatory effects in immunosuppressed primate recipients of porcine kidneys.

Results: Some degree of consumptive coagulopathy developed in both rhAT-treated (n=3) and untreated (n=3) primates.

How do general practitioners rate their relationship with gastroenterologists?

Background: Relations between general practitioners and the hospital consultants are often considered difficult, and occasionally generate conflicts, potentially affecting the patient management and healthcare system organisation. These views, however, have partly been contradicted by structured surveys and qualitative studies.

Aims: We conducted a survey on the general practitioners' opinions regarding their relations with the gastroenterological-endoscopy services in order to explore current attitudes, any negative aspects and assess scope for improvement.

Ureteral stenosis in HDAF pig-to-primate renal xenotransplantation: a phenomenon related to immunological events?

The aim of this study was to analyze the incidence of ureteral stenosis in a life-supporting human decay-accelerating factor (hDAF) transgenic pig-to-cynomolgus monkey kidney transplantation model and determine the role of possible immunological events in its pathogenesis. Thirty consecutive bi-nephrectomized cynomolgus monkeys received a kidney from hDAF transgenic pigs with or without a ureteral stent. Four monkeys were euthanized prematurely after transplantation.

Alterations in the coagulation profile in renal pig-to-monkey xenotransplantation.

Five monkey recipients of a porcine renal xenograft were studied to determine the relationship between fibrin formation in acute humoral xenograft rejection (AHXR) and procoagulant and anticoagulant factor levels to establish whether changes in coagulation parameters could be used to predict AHXR and determine whether AHXR is associated with overt disseminated intravascular coagulopathy (DIC) in this model. Variable degrees of compensated consumptive coagulopathy were observed in each primate. Elevated thrombin-antithrombin (TAT), F1+2 and D-dimer levels consistent with thrombin generation and fibrin formation were recorded.

Xenotransplantation, where do we stand?

Xenotransplantation is currently being investigated as a possible solution to the world-wide shortage of human organs. Several major advances have unquestionably been accomplished in the last decade in this field. These include an elucidation of the immunological mechanisms underlying the rejection of pig organs transplanted into primates, the generation of novel lines of genetically-engineered pigs that are more "compatible" with man and a better understanding of the risk of zoonosis related to the transmission of porcine endogenous retroviruses to primates.

Methotrexate for immunosuppression in life-supporting pig-to-cynomolgus monkey renal xenotransplantation.

Methotrexate (MTX) has been used successfully as an immunosuppressant in rodent xenotransplantation models, but the data generated so far with MTX in pig-to-baboon cardiac transplantation studies have been disappointing. The potential of this agent was consequently explored in a life-supporting pig-to-primate renal model using the cynomolgus monkey as the recipient species. Introductory in vitro and in vivo pharmacokinetic and pharmacodynamic studies with MTX were conducted in three cynomolgus monkeys.

Endoscopic treatment of upper airway and digestive tract lesions caused by caustic agents.

We present our experience in the endoscopic management of upper aerodigestive tract lesions caused by caustic agents. Between 1985 and 2000, 112 patients with upper airway and digestive tract lesions due to caustic agents were treated at the Airways Endoscopic Surgery Unit of Padua Hospital: 44 were male and 68 were female, and the median age was 42.6 years.

Pharmacokinetics of intraperitoneal hyperthermic perfusion with mitoxantrone in ovarian cancer.

Purpose: Theoretical data and experimental assumptions indicate that intraperitoneal hyperthermic chemotherapy may play a role in the treatment of peritoneal carcinomatosis. The feasibility, tolerability and pharmacokinetics of intraperitoneal hyperthermic perfusion with mitoxantrone were studied in patients with pretreated ovarian cancer.

Methods: After cytoreductive surgery, 11 patients underwent intraperitoneal hyperthermic perfusion with mitoxantrone.

Chemo-immunotherapy of advanced AIDS-related Kaposi's sarcoma.

Aims And Background: Kaposi's sarcoma (KS) is the most common neoplastic complication of HIV infection and AIDS. Multiple cytotoxic chemotherapy regimens have been used with various response rates. We have evaluated the efficacy and toxicity of low-dose chemotherapy in patients with poor-prognosis AIDS-related KS and the role of interferon alpha (IFN-alpha) in complete responders.

Carboplatin plus 5-fluorouracil and leucovorin in previously treated patients with metastatic breast cancer.

The commonly reported second-line chemotherapy regimens administered for metastatic breast cancer usually induce few responses, which last no more than 4 to 8 months. We used carboplatin 50 mg/m2 on days 2, 3, and 4 of each course, leucovorin 500 mg/m2 on days 1 through 5 in 30-minute infusions, and 5-fluorouracil (5-FU) 375 mg/m2 intravenous bolus 1 hour after each leucovorin dose to treat 32 patients with metastatic breast cancer. Six patients had previously received treatment with only one cytotoxic chemotherapy regimen, usually CMF (cyclophosphamide/methotrexate/5-FU).

Lymphomas in the elderly.

The elderly patients with lymphoma suffer from a relevant excess mortality, both during treatment and in the course of follow-up: various causes contribute, including: 1) "generational" mortality; 2) iatrogenic mortality due to unexpected organ/system fragility; 3) low remission rates, due to low tolerated doses and, 4) a high prevalence of second tumors. The difficulty in achieving high cure rates begins after age 50 and steadily increases for patients over 60, 70 and 80. Less aggressive staging procedures are justified, and the modern visualizing techniques provide alternatives to lymphangiography and laparosplenectomy.

A 5-day regimen of cyclophosphamide, adriamycin, platinum (CAP) in refractory breast cancer.

The activity of the association of cis-platinum with Adriamycin and cyclophosphamide (CAP), as "rescue" chemotherapy for the treatment of refractory and relapsing advanced breast cancer, is presented. Of 42 evaluable patients, previously treated with chemotherapy +/- hormone therapy, 4 (9.5%) achieved a complete response, 15 (35%) had a partial response (CR + PR = 45%).