Pharmacokinetics for once- versus twice-daily tacrolimus formulations in de novo kidney transplantation: a randomized, open-label trial.

Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC(0-24) of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC(0-24) and C(min) for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID.

Coronary artery calcium distribution and interscan measurement variability in end-stage renal and coronary heart disease patients.

BACKGROUND: Coronary heart disease patients and end-stage renal disease patients have been documented to have an increased amount of coronary artery calcifications (CAC). PURPOSE: To evaluate the distribution of CAC and its influence on interscan variability of measurement in end-stage renal disease and coronary heart disease patients, proven to have calcifications. MATERIAL AND METHODS: 69 patients having CAC, including 34 with coronary heart disease and 35 with end-stage renal disease, were scanned twice with multidetector-row computed tomography (MDCT). Amount of CAC was determined as the number of calcified lesions (CN), total calcium score (CS), calcium volume (CV), and calcium mass (CM). Distribution of CAC was evaluated on a per-patient basis as the median CS and CM of a single lesion. Density of the calcifications was calculated as the patient's CM divided by CV. RESULTS: The overall median CS was 457.2, and the median CM was 75.6 mg. There were no significant differences in the number of calcified lesions, CS, or CM between the two groups. Both CS and CM of a single lesion, as well as the mean calcium density were lower in renal disease patients (P<0.05) than in coronary heart disease subjects. The relative interscan variability of coronary calcium measurement was higher in the renal disease group (P<0.05). There was a negative correlation between the calcium concentration and the relative interscan variability. CONCLUSION: The results indicate that the coronary calcium distribution influences the measurement interscan reproducibility, and the distribution may differ between end-stage renal disease patients and coronary heart disease patients, reflecting the dissimilar nature of coronary calcifications in those groups.

Are we taking proper care of living donors? A follow-up study of living kidney donors in Poland and further management proposal.

OBJECTIVE: The first kidney transplantation was performed in Poland in 1966. Since that time approximately 11,000 patients have undergone the procedure, but most of them have received the kidney from deceased donors; only 342 procedures utilized living donors (LD; 2.7%). The aim of this study was to review the results of a LD follow-up in Poland. PATIENTS AND METHODS: A questionnaire was sent to 11 centers that had performed 197 LD kidney transplantations during the last 10 years. The donors, who were all genetically or emotionally related, were 23 to 61 years old. No donor showed an abnormality regarding cardiovascular function or metabolic abnormalities. RESULTS: The 6 centers that responded reported data on 118 donors. In 2 centers no donor follow-up was available. Eleven of 118 donors did not attend the control visits. Follow-up of the remaining donors ranged from 2 to 8 years. Four donors died at 4 to 5 years after nephrectomy due to cerebral hemorrhage, brain tumor, stomach cancer, or car accident. The overall mean serum creatinine had increased from 0.8 to 1.25 mg/dL, but 2 patients displayed a value >2 mg/dL. The calculated creatinine clearance (MDRD formula) had decreased from 95 to 65 mL/min (P < .05). In 3 donors proteinuria (>0.6 g/24 h) was observed at 3 to 5 years after donation. Of 3 patients who experienced mild hypertension, 2 required treatment. The remaining donors showed normal blood pressures. CONCLUSIONS: Since 2007, when the Living Donor Registry was introduced by law, transplant centers have been obliged to report data on each LD procedure together with follow-up data. All donors are life-insured (by Alianz SA) for 3 months from the time of transplantation. Stepwise interventional reno- and cardioprotection programs have been introduced after nephrectomy for LD, especially those with metabolic abnormalities at the time of donation.

Holistic Long-Term Care Over Elderly Kidney Transplant Recipients.

Kidney transplantation is an optimal method of renal replacement therapy in patients with phase V chronic kidney disease. Elderly patients (older than 60 years) with a kidney transplant create a significant and constantly growing pool of patients with this type of organ transplantation. In this group of patients, long-term care should be particularly stringent and vigilant. Apart from typical conditions associated with chronic kidney disease and possible post-transplant complications as well as side effects of immunosuppressive treatment, the patient also experiences changes and limitations associated with the progress of age and diseases typical for old age, characterized by a higher risk of infection, and changed pharmacokinetics/pharmacodynamics. Undoubtedly, patients should remain under the medical care of qualified transplantologists, but constant cooperation with a general practitioner and geriatrician would be of added value. Study results show that although most of the elderly kidney recipients have constant contact with their general practitioners, and almost half of them use private care, contribution of the geriatrician to the transplant care system is unsatisfactory, and elderly kidney recipients would expect more extensive outpatient care.

Guanylate cyclase activators influence reactivity of human mesenteric superior arteries retrieved and preserved in the same conditions as transplanted kidneys.

INTRODUCTION: This study sought to investigate the mechanisms of relaxation induced by the (nitric oxide (NO)-independent soluble guanylyl cyclase (sGC) stimulators 3-[5'-hydroxymethyl-2'-furyl]-1-benzylindazole (YC-1) in human mesenteric arteries relaxed and precontracted with 1 micromol/L 5-hydroxytryptamine (serotonin). MATERIAL AND METHODS: Human mesenteric arteries obtained during kidney retrieval were preserved in the same conditions as transplanted kidneys. All experiments were performed after reperfusion with Krebs buffer in 37 degrees C and 100% oxygen exposure. RESULTS: In endothelium-intact rings, YC-1 (0.001 to 30 mmol/L) caused concentration-dependent relaxation (pEC(50): 6.59 +/- 0.12), which shifted to the right in endothelium-denuded rings. The sGC inhibitor 1H- [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ 10 mmol/L) partially attenuated the maximal responses to YC-1 (E(max) = 51.30% +/- 3.70%; n = 6) and displaced its curve to the right in intact and denuded vessels. Both, the NO synthesis inhibitor N-nitro-L-arginine methyl ester (100 mmol/L) and the NO scavenger carboxy-2-[4-carboxyphenyl]-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (100 mmol/L) significantly reduced YC-1 relaxation. The sodium pump inhibitor ouabain (1 micromol/L) produced a greater decrease in the vasodilator response of YC-1 (E(max) = 18.7% +/- 4.55%; n = 9). ODQ (10 micromol/L) plus 1 mumol/L ouabain abolished the relaxant response of YC-1 (E(max) = 9.4% +/- 2.94%, n = 9). CONCLUSIONS: This study demonstrated that sodium pump stimulation by YC-1 as an additional mechanism of sGC activation independent of cGMP relaxed human mesenteric artery, including blockade of Ca(2+) influx. Furthermore, this study suggested an ability of NO to mediate relaxation of resistance-like arteries through the activation of soluble guanylate cyclase and K(+) channels.

Extreme attitudes toward organ transplantation: how do supporters and opponents of this method of treatment differ in Poland?

BACKGROUND: Many medical professionals share the opinion that the negative social attitudes toward transplantation are the basic cause of the deficit of organ from deceased donors. Although public opinion polls in Poland invariably reveal overall acceptance of transplantation, it is extremely difficult to procure organs. The purpose of this study was to compare the attitudes of supporters and opponents of organ transplantation. MATERIALS AND METHODS: In social psychology, attitude is defined as a relatively stable inclination toward a positive or negative relation to a person or an object. It was assumed that positive attitudes are favorable as regards transplantation, whereas negative attitudes constitute a social obstacle to this method of treatment. The survey conducted between May and August 2002 included a representative sample of 1000 Poles over 15 years of age. The first part of the survey measured the general attitude toward transplantation on a rating scale ranging from "definitely agree" to "definitely disagree." RESULTS: We distinguished two extreme attitudes, ie, supporters and opponents. CONCLUSIONS: The attitudes of supporters were mainly cognitive, whereas the attitudes of opponents were dominated by negative emotions associated with fear of death, psychological trauma, and physical injury which led to avoidance behavior, passive resistance, and selective and biased information processing. Opponents often concealed or belittled their standpoints and were reluctant to discuss transplantation issues. Their behavior was more passive, and their familiarity with the medical and legal aspects of transplantation was relatively poor compared with supporters.

Does the presence of unwanted dermal fibroblasts limit the usefulness of autologous epidermal keratinocyte grafts?

OBJECTIVES: Fibroblasts sometimes occur after enzymatic isolation of epidermis. They proliferate quickly, overgrowing the culture. A pure epithelial culture is essential for therapy using a keratinocyte graft. The aim of this study was to determine the possibility of fibroblast elimination from culture to prevent fibroblast overgrowth and obtain a pure monolayer of keratinocytes. MATERIAL AND METHODS: We analyzed three epidermal-derived cultures. Cells were cultured in medium contained Dulbecco's Modified Eagle Medium (DMEM) and Ham's F-12 at a 3:1 ratio with 5% autologous serum and additives. The epithelial culture was confirmed using pancytokeratin MMF. If fibroblast like cells were present, they were removed using 0.01% edetate disodium dihydrate (Na2EDDA). This procedure was repeated until we obtained pure primary keratinocyte cultures. RESULTS: Fibroblast detachment was observed after Na2EDDA treatment. The procedure was performed twice and pure primary cultures of keratinocyte were achieved in two cases. These two cultures maintained their epithelial-like morphology and cytokeratin expression. One culture was treated four times with Na2EDDA with no effect; the morphology of the cultures became fibroblast-like with no observed cytokeratin expression. CONCLUSIONS: Unwanted dermal fibroblasts can be separated from primary keratinocyte cultures during the first few days after the isolation. Cocultures of unwanted dermal fibroblasts and epidermal keratinocytes can be reverted to pure keratinocyte monolayers suitable as grafts for transplantation.

Superoxide anion as a marker of ischemia-reperfusion injury of the transplanted kidney.

Reactive oxygen species (ROS) are considered to be important factors involved in the pathophysiology of renal ischemia-reperfusion injury. ROS-induced alterations of proteins, carbohydrates, DNA, and lipid membranes lead to cell and organ dysfunction. Several antioxidant defense mechanisms exist to prevent or limit oxidant injury. Cellular Cu-Zn superoxide dismutase, catalase, and cellular glutathione peroxidase (cGSH-Px) are enzyme ROS scavengers, implicated in the protection against kidney damage resulting from ischemia-reperfusion injury. Reduced glutathione, a cosubstrate of cGSH-Px, have been shown to display a reductive properties without the contribution of enzymes. We examined superoxide anion (O(2)(-)) production by neutrophils, without and with stimulation using opsonized zymosan, in the whole blood of renal transplant patients before and after (5 and 15 minutes) reperfusion. The mean O(2)(-) concentration after reperfusion was statistically significantly higher than that before reperfusion.

Nitric oxide and thromboxane A2 modulate pulmonary pressure after ischemia and intestinal reperfusion.

INTRODUCTION: Nitric oxide (NO) and thromboxane A(2) (TxA(2)) are paracrine substances that likely contribute to IR-induced lung injury. This study examined the hypothesis that pulmonary vasoconstriction during ischemia is induced by NO synthesis and ischemia/reperfusion (IR)-induced TxA(2). METHODS: Wistar rats underwent 30 or 60 minute of intestinal ischemia with 60 minute of IR in situ. Sham-operated animals (Sham) served as the controls. After ischemia and IR or Sham, the pulmonary vessels were cannulated to perfuse the lungs with Krebs buffer in vitro. Pulmonary arterial (Ppa) and venous (Ppv) pressures were measured to calculate vascular resistance (Rt). RESULTS: After baseline measurements, the nonselective inhibitor (N(omega)-nitro-L-arginine methyl ester), the selective nNOS inhibitor 1-(2-trifluoromethylphenyl) imidazole (TRIM), TxA(2) synthase inhibitor imidazole or TxA(2)-receptor antagonist SQ-29,548 was added to the perfusate prior to measurements of Ppa, Ppv, and Ppc. The Rt was 73% greater in the injured group (P = .01). Pc of in the IR lungs was about twice that of controls (7.2 +/- 0.71 vs 2.43 +/- 0.36 mm Hg, respectively; P < .01). The nNOS inhibitor TRIM, imidazole, or SQ-29,548 reduced Rt by 45%, 33%, and 26%, respectively. IR-induced increases in Pc were reduced by addition of 500 mug/mL imidazole but not by lower doses of imidazole or SQ-29,548. CONCLUSIONS: IR-induced pulmonary dysfunction is caused by increased vascular resistance and increased perfusion pressure. These changes are, at least in part, due to the ongoing release of TxA(2). Administration of 8Br-cGMP protected against TxA(2)-induced vasoconstriction.

Benign Cutaneous Disease Among Polish Renal Transplant Recipients.

BACKGROUND: Organ transplant recipients are an at-risk group for skin cancers and benign cutaneous diseases. Immunosuppression type, dosage, and treatment length dictates the frequency of benign lesions. MATERIAL AND METHODS: Two hundred twenty-three consecutive adult renal transplant recipients (RTRs) were enrolled and screened for benign skin lesions. During examination, swabs, skin scrapings, and nail clippings were collected from any suspected areas infection and any cutaneous lesions marked for quality and quantity on a special questionnaire. The aim was to examine the prevalence of benign cutaneous disease and risk factors. RESULTS: Fungal infections were the most common infections found (60%), most commonly in the oral cavity (40.8%). Viral warts occurred in 18.4%, being significantly more common in those transplanted over 5 years (P = .002). Hypertrichosis was the most common pilosebaceous disorder found (P ≤ .001). Other iatrogenic cutaneous effects included purpura (50.2%), xerosis (41.2%), and gingival hyperplasia (28.2%), the latter strongly associated with cyclosporine (P = .0005). Seborrhoeic warts (23.8%) were most common in patients older than 50 years (P < .001). One-third of subjects had skin tags (31%). DISCUSSION: This is the largest study of the prevalence and type of non-malignant cutaneous diseases in Polish RTRs. We see increasing numbers of patients with long-term side effects from immunosuppressive therapy, and treatment, gender, age, and time since transplantation should be considered with new skin lesions in everyday practice with RTRs. CONCLUSIONS: The study group had a high prevalence of benign cutaneous diseases and these should not be overlooked as they can cause aesthetic problems and reduced quality of life.

Kidney preserving solutions containing lidocaine may increase urological complication rate after renal transplantation: an in vitro study.

OBJECTIVE: The frequency of urological complications after renal transplantation is up to 12%. Some authors consider that lidocaine addition to preservation solutions produces a favorable influence on allograft function. However, lidocaine may influence urinary tract epithelial cells. The aim of this work was to establish the influence of lidocaine on cultured primary rabbit urothelial cells (PRUC) as a tool to understand mechanisms of urological complications after kidney transplantation. DESIGN AND METHODS: A PRUC culture was established from an 8-month-old male rabbit bladder. The cells were cultured alone and then with in various concentrations of lidocaine for 24 hours or 1 hour. After an additional 24 hours, cell viability was assessed by the trypan blue exclusion test. Student's t test was used for statistical analysis, with significance set at P < .05. RESULTS: The cytotoxic effects of lidocaine on PRUC were concentration dependent. One-hour exposure of PRUC culture to 0.5 or 1.0% lidocaine decreased cell viability. Both lidocaine concentrations decreased cell viability in PRUC culture after a 24-hour incubation; even 0.25% lidocaine caused changes in the PRUC culture morphology after a 1-hour incubation. Cells became rounded and detached from the growth surface. No cells were observed in the monolayer after 1-hour incubation with 1% of lidocaine. CONCLUSIONS: The toxic effects of lidocaine on PRUC may forecast problems with supplementation of kidney preservation solutions, leading to impaired epithelial layer healing with an increased risk of urological complications.

Lipid metabolism in renal transplant patients receiving tacrolimus/sirolimus combination therapy.

INTRODUCTION: The administration of sirolimus has been reported to be associated with high serum cholesterol and high triglyceride values. In a large prospective, multicenter 6-month study in renal transplantation, basic parameters of lipid metabolism (total serum cholesterol and triglycerides) were systematically assessed in patients who received tacrolimus/mycophenolate mofetil/steroids (Tac/MMF), tacrolimus/0.5 mg sirolimus (SIR)/steroids (Tac/0.5SIR) on tacrolimus/2 mg sirolimus/steroids (Tac/2SIR). METHODS: For purposes of analysis, lipid parameters were classified using the National Kidney Foundation Dyslipidemia Classification definitions. RESULTS: Complete sets of data at all visits (baseline, months 1, 3, and 6) were available for 211 Tac/MMF, 210 Tac/0.5SIR, and 203 Tac/2SIR patients. Total serum cholesterol in the Tac/MMF group was 193.4 at baseline and 202.9 mg/dL at month 6. Values increased from 196 mg/dL to 212.5 mg/dL in Tac/0.5SIR and from 200 mg/dL to 230.5 mg/dL in Tac/2SIR. Differences in parameters between treatment groups were statistically significant (P < .05). Serum triglycerides decreased from baseline to 6 months in Tac/MMF, increased from 176.3 mg/dL (baseline) to 191.4 mg/dL (6 months) in Tac/0.5SIR and from 203 mg/dL to 255.3 mg/dL in Tac/2SIR. Parameters differed significantly between Tac/0.5SIR versus Tac/2SIR at P = .0069, and between Tac/MMF versus Tac/2SIR at P = .0013. In the Tac/2SIR group 36.5% had "high" serum cholesterol and 8.3% had "very high" triglyceride levels at 6 months. CONCLUSION: Total serum cholesterol levels were relatively stable and serum triglycerides decreased between baseline and month 6 using a Tac/MMF regimen. Contrastingly, the Tac/SIR combinations led to increased total cholesterol values (at both sirolimus dose levels) and Tac/2SIR also led to increased triglyceride levels.

Interpretation of the nonextensivity parameter q in some applications of tsallis statistics and Levy distributions

The nonextensivity parameter q occurring in some of the applications of Tsallis statistics (known also as index of the corresponding Levy distribution) is shown to be given, in the q>1 case, entirely by the fluctuations of the parameters of the usual exponential distribution.

Function, structure, and volume of thyroid gland following allogenic kidney transplantation.

The aim of the study was to assess the structure, volume, and function of the thyroid gland following kidney transplantation compared with those features of long-term transplant recipients as well as patients with normal native kidney function. Study group A consisted of 30 patients undergoing allogenic kidney transplantation, study group B included 30 long-term kidney transplant recipients who displayed stable renal function at 4 to 11 years following transplantation; control group C comprised 38 patients who were diagnosed or treated for reasons other than thyroid or renal insufficiency. Mean FT-3 concentrations in group A decreased from 2.19 pg/mL preoperatively to 1.52 pg/mL on the first posttransplantation day, returning to the preoperative values (2.06 pg/mL) at 30 days postoperatively. After 6 months the concentrations of thyroid hormones were similar to those among the long-term posttransplantation group (group B), although still lower than those in the control group. Mean thyroid volume in dialyzed patients was 17.10 mL; in the long-term group, 17.60 mL; and in the control group, 15.82 mL between groups that were not statistically significant. Abnormal structure of the thyroid gland was observed in 63% of group A (n = 19), 70% of group B (n = 21), and 29% of the control group. Significantly more abnormal thyroid gland structures were observed among dialyzed or transplanted patients. The thyroid volume was similar in all groups. Significant transient decrease in thyroid stimulating hormone (TSH) and free triidothyronine (FT-3) was not free thyroxine (FT-4) concentrations following kidney transplantation. Occasionally, increase accompanied by a change in FT-4 and TSH concentrations were observed, and antithyroid antibodies were detected only sporadically.

Vocational rehabilitation following kidney transplantation.

Successful kidney transplantation (KT) improves significantly the quality of life as compared with hemodialysis. Vocational rehabilitation and professional activity are the vital part of general rehabilitation and play an important role in determining the quality of life. The aim of this study was to evaluate the degree of vocational rehabilitation of the patients following allogenic kidney transplantation. 114 patients were questionnaired. Evaluation of the data revealed that only 31.6% of the study group returned to work despite good quality of life and satisfactory graft function of more than 75% of the KT patients. Factors influencing re-employment included gender, age and education level. Most of the patients were re-employed within 6 months following KT. In 78.9% of the cases formal disability status was not changed after KT and remained discrepant with good general condition and graft function. Results of the study allow authors to conclude that unless vocational rehabilitation of the KT patients is not improved, the chances of return to full social life given by KT are mostly wasted.

Prevalence of arterial hypertension following kidney transplantation--a multifactorial analysis.

Arterial hypertension is one of the most important factors leading to chronic graft nephropathy and causing cardiovascular complications following renal transplantation. Effective control of the blood pressure seems to be vital for satisfactory long-term graft and patient survival. The objective of the study was to evaluate possible factors associated with persistent or de novo hypertension in patients following allogenic cadaveric kidney transplantation. 325 patients with minimum follow-up period of 6 months and only on cyclosporine-based immunosuppression were analyzed. Two groups of patients were compared: group A included normotensive or "well controlled hypertension" patients while group B consisted of patients with uncontrolled hypertension. Results revealed that patients with ill-controlled or uncontrolled hypertension received kidneys from older donors, mean creatinine level within 6 months post-transplant was significantly higher and hypertension was associated with higher rate of urinary tract infections in this group.

Influence of ureterovesical anastomosis technique on the incidence of vesicoureteral reflux in renal transplant recipients.

Urological complications of allogenic kidney transplantation include vesicoureteral reflux which can result in graft threatening urinary tract infection. To prevent this complication several ureterovesical anastomosis techniques have been developed. Authors present a comparison of three different techniques: extravesical without antireflux mechanism, extravesical Witzel-Lich with antireflux mechanism and intravesical Laedbetter-Politano with antireflux mechanism. 39 patients were selected randomly from a cohort of 420 allogenic kidney recipients (follow up time 10-147 months). All patients had voiding cystography and urine culture performed. The incidence of vesicoureteral reflux varied from 13.3% to 50%, depending on the anastomosis technique. No correlation between type of anastomosis and urinary tract infection was found.

Perioperative single high dose ATG-Fresenius S administration as induction immunosuppressive therapy in cadaveric renal transplantation--preliminary results.

Monoclonal and polyclonal antilymphocyte antibodies have been used successfully in organ transplantation as induction therapy and in the treatment of acute graft rejection. Used for induction the medication is generally given for the first 7-10 days. The aim of this study was to assess the safety and efficacy of single high dose (9 mg/kg) ATG Fresenius S given perioperatively, before revascularization, to kidney allograft recipients. During last twelve months seventy six, first cadaveric kidney adult recipients were included into the study in two centers (center A-64, center B-12). All patients received triple drug immunosuppression (Neoral, steroids and Cellcept which was replaced by azathioprine after 4 months), and were randomized to receive ATG or not. The follow-up period ranged from 1 month up to 1 year. The preliminary results are very promising, the rejection rate in bolus group was significantly lower than in control. No significant side effects or serious adverse events in both groups were observed.

Freedom from rejection and stable kidney function are excellent criteria for steroid withdrawal in tacrolimus-treated kidney transplant recipients.

OBJECTIVES: This prospective, randomized, multicentre study investigated the efficacy and safety of two tacrolimus-based regimens and their potential to withdraw steroids. METHODS: In total 489 patients were randomised to receive either tacrolimus and MMF (n = 243) or tacrolimus and azathioprine (n = 246) concomitantly with steroids in both treatment groups. The initial oral dose of tacrolimus was 0.2 mg/kg/day, MMF dose was 1 g/day, azathioprine was administered at 1-2 mg/day. Steroids were tapered from 20 mg/day to 5 mg/day. From month 3 onwards, steroids were withdrawn in patients who were free from steroid-resistant rejection and who had serum creatinine concentrations < 160 mumol/L. Study duration was 6 months. RESULTS: Patient survival at month 6 was 98.3% (Tac/MMF/S) and 98.4% (Tac/Aza/S), graft survival at 6 month was 95.0% (Tac/MMF/S) and 93.5% (Tac/Aza/S). The 6-month incidences of biopsy-proven acute rejection were 18.9% (Tac/MMF/S) compared with 26.8% (Tac/Aza/S), p = 0.038. The 6-month incidences of steroid-resistant acute rejection were 2.1% (Tac/MMF/S) and 4.9% (Tac/Aza/S), p = ns. At the end of month 3, steroid withdrawal was performed in 60.5% (Tac/MMF/S) and 48.8% (Tac/Aza/S) of patients, p < 0.01. During months 4-6, 2.7% of patients in the Tac/MMF group had a biopsy-confirmed acute rejection compared with 0.8% of patients in the Tac/Aza group. In patients who continued to receive steroids, the incidences of biopsy-proven acute rejections during months 4-6 were 3.5% (Tac/MMF/S) and 7.1% (Tac/Aza/S). At study end, the steroid-free patients had an excellent kidney function, the median serum creatinine concentration was 119.5 mumol/L (Tac/MMF) and 115.1 mumol/L (Tac/Aza); the median serum creatinine of the total study group was 130.5 mumol/L (Tac/MMF/S) and 132.8 mumol/L (Tac/Aza/S). CONCLUSION: Both tacrolimus regimens are efficacious and safe. The combination of Tacrolimus and MMF achieved a lower rejection rate and permitted a higher proportion of steroid-free patients. The overall incidence of acute rejection was low and kidney function was good.

[Estimation of physical exertion by the AET ergonomic job description]. / Ocena obciazenia fizycznego z zastosowaniem ergonomicznej analizy pracy AET.

The study has been aimed at showing the advantages of using the AET ergonomic job description for estimation of physical workload, as compared to the traditional methods in which the estimates are made on the basis of the value of energy expenditure, static load and motion monotypicity. From tests on employees at 28 workposts it has been found that by analysing 17 factors involved in the overall estimate of physical workload according to AET, it is possible to characterize the work more precisely. The results of the tests indicate that AET estimates of heavy dynamic work are strongly correlated with the size of energy expenditure, whereas the estimation of body position--with the estimate of static load and the frequency estimate--with the estimate of motion monotypicity. New possibilities, with regard to the traditional method of physical workload estimation, are opened up by the AET method in relation to light dynamic work and static effort. The physical workload rate, calculated according to the AET method as the total of 17 elements estimated, does not differentiate the values of the workloads at individual workposts and, therefore, requires physiological verification.