Codeine-induced histamine release in intact human skin monitored by skin microdialysis technique: comparison ofintradermal injections with an atraumatic intraprobe drug delivery system

Background The skin microdiallysis technique makes it possible to measure histamine release in intact human skin in vivo directly. In this study we have used the microdialysis technique to characterize histamine release by codeine after intracutaneous injectioin and following skin challenge by a novel atraumatic delivery technique. Objective The purpose of the study was to compare histamine release in human skin by codeine. delivered by an intraprobe drug delivery system (IPD) and intracutaneous injections (ICT), with respect to dose-response relations, kinetics of histamine appearance and decay, corelations between histamine release and skin respones, and reproducibility. Methods Hollow dialysis fibres were inserted intradermally in 12 healthy subjects. Twelve fibres were inserted in each subjects, six fibres in each arm. Each fibre was perfused at a rate of 3 μL/min, and samples were collected in 2 min fractions. By the IPD technique, codeine was administrered to the skin by adding codeine to the perfusion medium. Sequential IPD challenges were performed in one arm. and ICTs were done on the other arm. Results Sixfold serial dilutions of codeine (0.01-3 mg/mL) caused a significant doserelated histamine release by ICT and IPD. Peak histamine release was found within the first 4 min after skin challenge by ICT and IPD, followed by a fast decline with a dialysate histamine half life of approximately 2-3 min. Peak hisamine release was linearly correlates with cumulative release of the 20 min sampling period, and histamine release correlated with weal soze. The coefficient of variation on peak histamine releae was 18.9% and 4.8% for codeine ICT and IPD, respectively. Conclusioin We have described in detail codeine-induced histamine release in intact human skin in vivo by the microdialysis technique. It was possible to administer codeine atraumaticallyl to the skin by intraprobe delivery. The skin microdialysis codeine atraumaticallly to the skin by intraprobe delivery. The skin microdialysis technique opens up possibilities for measurement of infllammatory mediators release in normal and diseases skin, and it will be possible to deliver immunopharmacologically active drugsto the skin by intraprobe delivery.     

Interstitial and vascular pancreas rejection in relation to graft survival

To examine the incidence of interstitial and vascular rejection in pancreas allografts and its impact on graft survival, we studied 36 percutaneous pancreas biopsies and 10 pancreas transplantectomy specimens from 32 patients who had undergone simultaneous pancreas-kidney transplantation. Interstitial rejection (IR) was predominantly found in the biopsies, while vascular rejection (VR) was most prominent in the transplantectomies. Pancreas graft survival was significantly decreased for pancreas grafts that had suffered from vascular rejection when compared to those with only interstitial rejection. Potential rejection markers, i. e., serum amylase, glucose, creatinine, and urinary amylase, did not correlate with histological signs of rejection, although increased levels of serum amylase were, in all but one case, associated with rejection.We conclude that a percutaneous pancreas biopsy remains the most reliable method to determine pancreas rejection, and that by distinguishing between IR andVR, a pancreas biopsy may provide important diagnostic as well as prognostic information. Received: 6 March 1997 Received after revision: 5 June 1997 Accepted: 30 June 1997     

Percutaneous technique for venovenous bypass including a heat exchanger is safe and reliable in liver transplantation

We have introduced and evaluated several modifications of the conventional venovenous bypass (VVBP) in 29 adult patients undergoing liver transplantation (OLT). A percutaneous technique for insertion of a jugular venous return cannula and a femoral vein cannula was applied. The inferior mesenteric vein (IMV) was used for splanchnic decompression, which facilitated dissection of the recipient liver and allowed portal anastomosis to be performed without disconnecting the portal bypass. A heat exchanger was introduced into the bypass circuit to prevent heat loss. The percutaneous technique prevented complications related to dissection in the axilla and groin. Hemodynamic characteristics corresponded to those found using the traditional technique. Complications related to the VVBP were seen in only one patient in whom the femoral catheter was accidentally introduced into the femoral artery. We conclude that percutaneous cannulas, use of the IMV for splanchnic decompression and the introduction of a heat exchanger offer significant benefits and that they are safe and reliable. Received: 23 August 1996 Received after revision: 14 January 1997 Accepted: 27 January 1997     

Is obesity still a risk factor in renal transplantation?

At our center, since 1982, a body mass index (BMI) of less than 30 has been a prerequisite for placing a patient on the waiting list for renal transplantation. This decision was made because obese transplant recipients seemed to have a less than favorable post-transplant outcome. The aim of this study was to evaluate whether this requirement is still justified. Forty-six patients with a BMI above 30 underwent primary cadaveric renal transplantation between 1972 and 1993. For each of these obese patients, five consecutive non-obese (BMI 20–25) control patients were selected. Patient and graft survival, causes of graft loss, and acute rejection rate were evaluated for the two patient groups before and after the year 1982. Within the first 30 post-transplant days, one patient (2 %) and 11 grafts (24 %) were lost in the group of obese patients whereas seven patients (3 %) and 36 grafts (16 %) were lost in the control group. Among the obese patients, renal circulatory complications were a major cause of graft loss. In the period 1973–1981, the 1-year patient survival rate was 65 % among obese patients versus 75 % among controls from 1982 to 1993, this was 90 % versus 93 %. From 1973 to 1981, the 1-year graft survival rate was 25 % among obese patients versus 53 % among controls (P < 0.05); from 1982 to 1993, it was 68 % versus 84 % (P = NS). Multivariate analysis showed that the immunosuppressive regimen, age of the patient, BMI, and cold ischemia time of the graft had a significant influence on graft survival. The acute rejection rate within the first 30 days was 28 % among obese patients and 35 % among controls (P = NS). We conclude that a BMI below or equal to 30 is still justified as a prerequisite for placement on the waiting list for renal transplantation, for despite an overall improvement, the outcome of renal transplantation in obese patients remains worse than that in non-obese patients. Received: 3 February 1997 Received after revision: 4 April 1997 Accepted: 8 April 1997     

The induction of operational tolerance is not prevented by simultaneous administration of cyclosporin A1

In this study, the effect of combining anti-CD4 monoclonal antibody (mAb) and cyclosporin (CyA) therapy at the time of transplantation was examined. A mouse cardiac allograft model was used. Anti-CD4 mAb administered perioperatively induces long-term survival. The addition of a short course of CyA given subcutaneously in a regimen of either a high-dose treatment or a standard dose treatment to the anti-CD4 mAb treatment protocol did not have a detrimental effect on graft survival. Despite having no significant effect on graft survival, the addition of CyA to the treatment protocol did result in a significant decrease in the level of IL-2 present in the hearts 7 days after transplantation. The decrease in IL-2 production was directly related to the presence of CyA in vivo. When CyA treatment was continued throughout the period during which unresponsiveness to the graft is induced by anti-CD4 mAb therapy, 50 % of the grafted hearts were rejected once the CyA was discontinued. In conclusion, the combined use of anti-CD4 mAb therapy and CyA did not have a negative effect on graft survival in this model when the two agents were used concurrently at the time of transplantation. Received: 2 October 1996 Received after revision: 31 January 1997 Accepted: 5 February 1997     

Validation of impedance cardiography measurements of cardiac output during limited exercise in heart transplant recipients

Abstract. Twenty-one patients were studied at rest and during exercise after heart transplantation to compare cardiac output measured by thermodilution and impedance cardiography. Exercise was performed on a bicycle ergometer over a limited range of work load (25 and 50 watt) whilst metabolic gas exchange was recorded. One patient was studied at rest whilst his circulation was maintained by a Jarvik-7 artificial heart. The values of cardiac output measured by impedance cardiography corresponded closely with the flow rate from the artificial heart. There was also close agreement between the impedance and thermodilution measurements of cardiac output at rest and during exercise. Both measurements followed the changes in heart rate and oxygen consumption. Both thermodilution and impedance cardiography methods elicited good reproducibility of cardiac output measurements at rest and during exercise. These observations suggest that the noninvasive and continuous record of cardiac output obtained by impedance cardiography can be used for the postoperative monitoring of heart transplant recipients.     

THE INTERACTION BETWEEN ENALAPRILAT AND SELECTED α-ADRENOCEPTOR ANTAGONISTS IN ISOLATED RAT TAIL ARTERIES

1. Isolated perfused rat tail artery preparations were used to investigate the effects of the angiotensin converting enzyme inhibitor enalaprilat on the actions of a series of α-adrenoceptor antagonists. The agonist used was phenylephrine. 2. Enalaprilat (1 μmol/L) potentiated the competitive α₁-adrenoceptor antagonist actions of phentolamine (10–100 nmol/L) and yohimbine (0.3–3.0 μmol/L) as well as the non-competitive antagonist action of phenoxybenzamine (50–100 pmol/L). 3. The competitive α₁-adrenoceptor antagonist action of prazosin (1–10 nmol/L) was not affected by enalaprilat. 4. For the competitive α₁-adrenoceptor antagonists, including prazosin, there appeared to be an inverse relationship between antagonist potency and the extent of potentiation by enalaprilat. 5. The results support the hypothesis and angiotensin II modulates vascular smooth muscle α₁-adrenoceptor function.     

Treatment of gingival lichen with free palatal grafts

BACKGROUND: Recalcitrant gingival erythematous lichen planus/lichenoid lesions comprise a considerable therapeutic problem. The objective of this study was to evaluate the therapeutic effect of grafting keratinized oral palatal mucosa to the sites of gingival lichen. METHODS: In 12 patients 20 grafts were transplanted to buccal gingival lesions. Mean age of the patients was 59.8 +/- 7.1 years (range 46-71 years). The mean observation time was 32 +/- 32.7 months (range 5-97 months). RESULTS: On a 4-point clinical grade scale (0-3), 12 (60%) transplants showed complete healing grade 3, six (30%) grade 2 and two (10%) grade 1. CONCLUSIONS: Using oral mucosal grafts from the palatal mucosa for the treatment of recalcitrant erythematous gingival lichen planus/lichenoid lesions seems to be a promising treatment modality.     

Treatment of hepatitis B and C after liver transplantation. Part 2, hepatitis C

Abstract End-stage liver disease caused by the hepatitis C virus is a major indication for liver transplantation. However, recurrence of hepatitis in the graft is a major issue. HCV re-infection after transplantation is almost constant, and recent data confirm that it significantly impairs patient and graft survival. Factors that may influence disease severity and consequent progression of HCV graft injury remain unclear. Chronic HCV infection develops in 60%–80% of patients, and 6%–28% ultimately progress to cirrhosis within 5 years. Pre-transplantation antiviral treatment is not easily related to poor tolerance. Attempts to administer prophylactic post-transplantation antiviral treatment are under evaluation but are limited by antiviral drug side effects. Treatment of established graft lesions with interferon or ribavirin as single agents has been disappointing. Combination therapy gave promising results, with sustained virological response in 25% of patients, but indications, modality and duration of treatment should be assessed.     

Clinicopathological study of vesicoureteral reflux (VUR)-associated pyelonephritis in renal transplantation

Abstract:  We retrospectively studied the occurrence of vesicoureteral reflux (VUR)-associated pyelonephritis using renal biopsies obtained from the transplanted kidneys, and correlated the histological changes with clinical parameters. Out of a total of 131 renal biopsies performed between 1990 and 2001 on renal transplant patients at the department of Urology of Nagasaki University Graduate School of Biomedical Sciences, 12 patients showed pyuria more than twice in a single year. Seven of these 12 patients were available for determining VUR by voiding cystourethrography (VCUG). Cystoureterography demonstrated VUR in three of seven studied patients with pyuria. A histopathological examination revealed dilatation of both proximal and distal tubules in renal biopsies of transplant patients with VUR, compared to renal biopsies of transplant patients without VUR, or non-transplanted patients with thin membrane disease. One of the patients with VUR showed advanced features of chronic pyelonephritis in four consecutive biopsies at different time points, suggesting a late stage of reflux nephropathy in the transplanted kidney. We conclude from our study that the occurrence of VUR-related pyelonephritis may be one of the important long-term complications in the survival of renal allografts.