In situ elongation patch in right kidney transplantation.

BACKGROUND: A short right renal vein complicates transplantation causing traction and difficulties during anastomosis. When we perform a kidney transplantation from a cadaveric donor, this problem may be resolved by using the vena cava to create a venous duct. This elongation technique is proposed to be performed during bench surgery. We propose a small change in the technique: execution of an "elongation patch" during harvesting and under cold perfusion. MATERIALS AND METHODS: From January 2004 to June 2006, we performed 12 in situ (during the harvesting procedure) vena cava elongation patches. In these cases, the right renal vein was too short. The elongation patch was used in only 8 transplantations. In the other 4 cases we sacrificed the patch to perform a direct venous anastomosis due to favorable recipient anatomical characteristics. RESULTS: The 8 transplantations performed with the elongation patch did not show vascular complications and the venous anastomosis was easy to perform. CONCLUSIONS: The "extension patch" was not associated with a greater incidence of vascular complications. Using the elongation patch during the harvest showed some advantages: performed during cold perfusion with a reduction in bench ischemia; the anatomical relationships are preserved so we can perform a calibrated suture; the perfusion of the organ allows us to observe the integrity of the anastomosis. This technique did not significantly increase the harvesting time.

Older kidneys donor transplantation: five years' experience without biopsy and using clinical laboratory and macroscopic anatomy evaluation.

INTRODUCTION: The exponential increase in organ demand is not associated with a similar increase of available kidneys. This emergency led to expanded criteria to consider a kidney transplantable. The aim of this retrospective study was to explain our use of older donor kidneys without biopsy. MATERIALS AND METHODS: Between 2000 and 2005, 58 older kidneys were harvested: 27 were transplanted in our center; 13 were discarded; and 18 were transplanted in other centers. We considered 3 factors to define kidney quality: macroscopic anatomy, multiple factors linked to the donor, and clinical-laboratory data. After transplantation, we observed the patients for at least 1 year and up to 6 years. DISCUSSION: At 1 year, 24/27 (89%) patients had a functional kidney, 2 patients showed an initial renal failure and 1 patient lost the kidney. At maximum follow-up, 19 patients (70%) had functional kidneys, 4 with initial renal failure. These results compared with the kidneys harvested using Standard Donor Kidney Criteria are acceptable. Obviously we need long-term follow-up to increase, the amount of data and obtain a definitive outcome. CONCLUSION: Biopsy is the gold standard for the definition of an older kidney's quality. When a biopsy is not feasible, the study of the macroscopic anatomy the kidney's donor and of some donor's parameters represent an acceptable biopsy alternative, being able to rescue some organs that would be otherwise lost.

Gemtuzumab ozogamicin with cytarabine and mitoxantrone as a third-line treatment in a poor prognosis group of adult acute myeloid leukemia patients: a single-center experience.

We analyzed the safety and efficacy of gemtuzumab ozogamicin (GO) combined with cytarabine and mitoxantrone in the treatment of 21 patients with acute myeloid leukemia (11 refractory and 10 in second relapse). Patients' median age was 52 years (range 36-68); all patients had previously been treated with anthracycline-containing regimens (daunorubicin and idarubicin). GO at a dosage of 3 mg/m2 was administered as a 2-h intravenous infusion on days 1 and 14, cytarabine at 100 mg/m2 on days 1-7, and mitoxantrone at 12 mg/m2 on days 1-3. Infusion-related events were observed in 15 of 21 (71.4%) patients. The incidence of grade 1 or 2 elevations of bilirubin and hepatic transaminases was 4 of 21 (19%) and 3 of 21 (14.2%). In response to chemotherapy, 2 of 21 (9.5%) achieved complete remission and 2 of 21 (9.5%) achieved complete remission with incomplete platelet recovery, with an overall remission rate of 4 of 21(19%); median survival of these 4 patients was 7 months. Four of 21 patients (19%) died during aplasia after chemotherapy; no veno-occlusive disease occurred. No treatment-related cardiotoxicity or cerebellar toxicity was observed. In our experience, the addition of GO to mitoxantrone and cytarabine is feasible in refractory or second relapse acute myeloid leukemia patients but yields a low response rate when used as a third-line treatment.

Difficult vascular conditions in kidney transplantation.

The new dialytic and medical therapies have improved the survival of uremic patients and their preservation of a efficacious clinical condition so as to warrant suitability for transplantation, even after a long period of dialysis. In addition, today the use of a "marginal donor" and "marginal kidney" are often used to increase the pool of available organs, so that the surgeon must face more technical difficulties than in the past; anomalies of the donor kidney, harvesting and bench surgery damages, as well as vascular pathologies in the recipient. A review of our 151 renal transplantations from January 1999 to May 2003 showed that it was often possible to overcome these technical difficulties yielding good results. This work sought to demonstrate that neither "marginal donor"/"marginal kidney" used to expand donor pool nor recipient vascular pathologies should be considered transplant contraindications. Knowledge of various technical options and the ability to put them rapidly into practice are necessary to use any organ.

Healing of surgical incision in kidney transplantation: a single transplant center's experience.

INTRODUCTION: Impaired healing of the surgical incision represents a common complication after kidney transplantation. We led a retrospective study seeking to understand the factors linked to these complications and reasons for their reduction during the last year. PATIENTS AND METHODS: From January 2000 to April 2004, 170 consecutive kidney transplantations were performed in a homogenous patient population. We evaluated the influence of following factors to determine impaired healing of the incision: antirejection drugs, overweight/obesity, age, delayed graft function (DGF), diabetes, and abdominal wall reconstruction technique. RESULTS: Among 165 patients we observed 26 (15.76%) cases of impaired healing of the surgical incision: 17 (65,38%) with first-level and nine with second-level wound complications. CONCLUSIONS: Impaired healing of the surgical incision influences the outcome of kidney transplant patients. In our study we observed that cyclosporine and tacrolimus similary affected the incision's healing. It was not possible to evaluate the role of basiliximab. A univariate analysis of the factors related to complications revealed overweight and DGF. However, all patients developing second-level complications showed more risk factors. Patients who had not had reconstruction of the muscle layers showed a greater incidence of surgical complications, whereas patients who had skin sutured with an intradermic technique did not show an increased risk.

A conjugate of prednisolone with albumin is pharmacologically active in macrophages.

In order to selectively deliver prednisolone to macrophages, this drug was coupled to human albumin. In experiments in vitro the conjugate entered into macrophages in much higher amounts than in fibroblasts; in the former cells it was pharmacologically active as demonstrated by the inhibition of prostaglandin E2 and thromboxane A2 production. Prednisolone-albumin conjugate might be useful in research on steroids; moreover in some pathological conditions it might produce the therapeutic effects of these drugs without causing their side effects.

Angiotensin converting enzyme inhibitors: animal experiments suggest a new pharmacological treatment for alcohol abuse in humans.

The prevalence of heavy alcohol consumption is a major problem of increasing proportions throughout the world. Although alcohol sensitizing drugs and more recently serotonin uptake inhibitors are drug interventions with some following, their long term beneficial consequences have yet to be demonstrated. In recent years, we have demonstrated that manipulating activity in the renin-angiotensin system will dramatically alter voluntary alcohol consumption in rats. Based on these findings, the present study evaluated the ability of a class of drugs known as the angiotensin converting enzyme inhibitors to reduce voluntary alcohol drinking in laboratory animals. These drugs prevent the conversion of angiotensin I to angiotensin II. They have been licensed for use in Europe and North America and are indicated in the treatment of hypertension. Our experiments showed that both captopril (Capoten, Squibb) and enalapril (Vasotec, Merck Sharpe & Dohme) can reduce alcohol drinking in both normotensive and hypertensive animals regardless of whether the pattern of intake is in a bout or of a less exaggerated nature. Furthermore, this change in alcohol intake can occur without concomitant changes in blood pressure, plasma renin activity, overall fluid balance, or the distribution and metabolism of alcohol. Taken together these findings suggest that the angiotensin converting enzyme inhibitors should be evaluated in a clinical setting for they may prove to be a useful new treatment or treatment adjunct for alcohol abuse in humans.

Targeting of antiviral drugs bound to protein carriers.

The value of antiviral drugs would be improved by their selective delivery into infected cells. This goal can be achieved by conjugating the drug to a protein which is taken up specifically by the cells where the virus grows. Conjugates will be pharmacologically effective in these cells if the bond linking the drug to the carrier does not suppress the activity of the drug or if the bond is broken down with consequent intracellular release of the drug. Experiments on this approach to antiviral chemotherapy have been directed mainly at selectively delivering antiviral agents into hepatocytes in order to increase their chemotherapeutic index in the treatment of chronic hepatitis B.

Conjugates of ara-AMP with lactosaminated albumin: a study on their immunogenicity in mouse and rat.

Complexes of albumin with oligosaccharides have been successfully employed in experimental chemotherapy as hepatotropic carriers of antiviral drugs or as vectors of anticancer-agents, but their clinical use is hampered by an immune response they might evoke. In the present experiments we have studied the humoral immunogenicity of conjugates of 9-beta-D-arabinofuranosyl adenine 5'-monophosphate (ara-AMP) with lactosaminated albumin (L-SA), in mice and rats. These complexes were prepared with the aim of increasing the chemotherapeutic index of ara-AMP in the treatment of chronic hepatitis B virus (HBV) infection. L-SA-ara-AMP conjugates prepared with heterologous albumin produced antibodies in mice and rats when repeatedly injected intraperitoneally. The same conjugates prepared with homologous albumin induced only low amounts of antibodies, when given by repeated intraperitoneal injection, whereas they did not evoke antibodies in mice and were tolerogenic in rats when administered repeatedly by the intravenous route. These results suggest that in a clinical use of drug conjugates prepared with oligosaccharide-albumin complexes the risk of an immune response can be reduced by employing human albumin and by injecting the conjugates by the intravenous route.

Distribution of a conjugate of 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) with lactosaminated albumin in parenchymal and sinusoidal cells of rat liver.

9-beta-D-Arabinofuranosyladenine 5'-monophosphate (ara-AMP) coupled to lactosaminated human albumin (L-HSA), injected i.v. into rats, selectively enters the liver. The conjugate concentration in parenchymal and sinusoidal hepatic cells, isolated by collagenase perfusion, was found to be practically equal in both cell types. This indicates that the high uptake of L-HSA-ara-AMP complex by the whole liver also corresponds to a high conjugate concentration in hepatocytes where ara-AMP should be targeted in order to increase its chemotherapeutic index in chronic hepatitis B treatment.

Galactosylated poly(L-lysine) as a hepatotropic carrier of 9-beta-D-arabinofuranosyladenine 5'-monophosphate.

D-Galactopyranosyl residues were coupled to poly(L-lysine) and the antiviral agents arabinofuranosyladenine 5'-monophosphate (ara-AMP) and acyclovir were conjugated with this glycosylated polymer. In mice the ara-AMP conjugate accomplished a selective drug delivery to liver cells.

Drug targeting in antiviral chemotherapy. A chemically stable conjugate of 9-beta-D-arabinofuranosyl-adenine 5'-monophosphate with lactosaminated albumin accomplishes a selective delivery of the drug to liver cells.

With the aim of improving the chemotherapeutic index of 9-beta-D-arabinofuranosyl-adenine 5' monophosphate (ara-AMP) in the treatment of chronic hepatitis B, this drug was conjugated with lactosaminated serum albumin (L-SA), a neoglycoprotein which only enters into hepatocytes. We used a L-SA-ara-AMP conjugate which, in contrast to those previously employed, has the advantage of remaining soluble after lyophilization. We found in mice that: (I) this new conjugate was quite stable in the bloodstream where only a small part of ara-AMP was released; (II) after administration of the conjugate labelled in the drug moiety both acid insoluble and soluble radioactivities were several times higher in liver than in other organs; (III) in mice with Ectromelia virus hepatitis, the conjugate inhibited virus DNA synthesis in liver without affecting cellular DNA synthesis in intestine and bone marrow; (IV) the conjugate did not display any recognizable sign of acute toxicity even at doses several fold higher than those pharmacologically active; and (V) when prepared with homologous albumin it was not immunogenic.