Left Ventricular Mass Is Associated With Ventricular Repolarization Heterogeneity One Year After Renal Transplantation

Ventricular repolarization heterogeneity (VRH) is associated with the risk of arrhythmia and cardiac death. This study investigated the association between VRH and left ventricular mass (LVM) in renal transplant recipients 1 year after transplantation. Echocardiography and 5-min 12-lead electrocardiogram were recorded and GFR was estimated (eGFR) in 68 nondiabetic patients. Beat-to-beat QT interval variability algorithm was used to calculate SDNN-QT and rMSSD-QT indices of VRH. To quantify QT interval variability relative to heart rate fluctuations, QTRR index was calculated. Left ventricular hypertrophy (LVH) was present in 44 patients (65%). LVM and incidence of LVH were increased in 28 patients with eGFR <60 mL/min/1.73 m² compared with 40 patients with eGFR ≥60 mL/min/1.73 m² (248 ± 61 g and 86% vs. 210 ± 46 g and 50%, respectively; p < 0.01). A direct correlation was found between LVM and SDNN-QT (R = 0.47, R²= 0.23; p < 0.001), rMSSD-QT (R = 0.27; R²= 0.10; p = 0.034), and QTRR (R = 0.55; R²= 0.31; p < 0.001) indices. In conclusion, greater LVM is associated with increased VRH in renal transplant recipients, providing a link with the high risk of arrhythmia and cardiac death, specifically in patients with decreased graft function .     

Estimation of glomerular filtration rate in South Asian healthy adult kidney donors

Aim:   We evaluated the performance of serum creatinine based equations to estimate glomerular filtration rate (GFR) in South Asian healthy renal donors.
Methods:   GFR by 99mTc-diethylenetriamine pentaacetic acid (DTPA) renogram (mGFR) in 599 renal donors was measured. GFR was estimated using a six variable modification of diet in renal disease formula (MDRD1), a four variable MDRD formula (MDRD2), Cockcroft-Gault creatinine clearance (CG CrCl), Cockcroft-Gault glomerular filtration rate (CG GFR) and the Mayo Clinic formula (Mayo GFR). The performance of various prediction equations was compared for global bias, precision (R²) and accuracy (percentage of estimated GFR (eGFR) falling within 15% and 30% of mGFR).
Results:   The mean age was 37.4 ± 11 years and 48.2% were male. The mGFR was 95.5 ± 11.6 mL/min per 1.73 m². The bias (mL/min per 1.73 m²) was 7.5 ± 0.9, −9.0 ± 0.75, 13.1 ± 0.9, 7.5 ± 0.9 and 23.4 ± 0.76 for CG CrCl, CG GFR, MDRD1, MDRD2 and Mayo GFR, respectively. R² was 0.082 for CG CrCl and MDRD1, 0.081 for CG GFR and MDRD2 and 0.045 for Mayo GFR. The percentages of eGFR falling within 15% and 30% of mGFR were 50.5 and 80.1 for CG CrCl, 65.8 and 84 for CG GFR, 50 and 74 for MDRD1, 54.3 and 80.1 for MDRD2 and 32 and 63.4 for Mayo GFR. Overall CG GFR performed better in estimating GFR in all subjects.
Conclusion:   The CG GFR equation was better than other equations to estimate GFR in South Asian healthy renal donors. We propose a new equation derived from the regression model in our study population to estimate GFR in a South Asian healthy adult population.     

Assessing Glomerular Filtration Rate by Estimation Equations in Kidney Transplant Recipients

Surveillance of glomerular filtration rate (GFR) is crucial in the management of kidney transplant recipients. With especial emphasis on serum creatinine (SCr) calibration assay, we assessed the performance of estimation equations as compared to iothalamate GFR (iGFR) in 209 patients using the modification of diet in renal disease (MDRD), Nankivell and Cockcroft-Gault methods. Fifty-five percent of patients were treated with a calcineurin inhibitor (CNI) and all were taken trimethroprim-sulfametoxazole at the time of SCr measurement. The mean iGFR was 44 ± 26 mL/min/1.73 m². The MDRD equation showed a median difference of 0.9 mL/min/1.73 m² with 53% of estimated GFR within 20% of iGFR. Median differences were 7.5 and 7.0 mL/min/1.73 m² for Nankivell and Cockcroft-Gault formulas, respectively. The accuracy of the Nankivell and Cockcroft-Gault formulas was such that only 38% and 37% of estimations, respectively, fell within 20% of iGFR. The performance of all equations was not uniform throughout the whole range of GFR, with some deterioration at the extremes of GFR levels. In addition, good performance of the MDRD equation was seen in subjects taking CNI. In conclusion, the overall performance of the MDRD equation was superior to the Nankivell and Cockcroft-Gault formulas in renal transplant recipients including subjects treated with CNI.     

Beta-Trace Protein-Based Equations for Calculation of GFR in Renal Transplant Recipients

Recently, we showed that serum beta-trace protein (BTP) is an alternative marker of glomerular filtration rate (GFR) in renal transplant recipients (RTR). We have now developed three BTP-based GFR formulae derived by multiple regression analyses from the patients who had participated in that study. Currently, we validated the diagnostic performance of these BTP-formulae in 102 consecutive RTR who underwent a technetium diethylenetriamine pentaacetic acid (DTPA) clearance for GFR measurement in comparison to the re-expressed Modification of Diet in Renal Disease (MDRD) equation and a recently proposed BTP-based equation (referred to as 'White equation').
The best-performing BTP formula was found to be: GFR = 89.85 × BTP^−0.5541× urea^−0.3018. This equation estimated true GFR virtually without bias (+0.43 mL/min/1.73 m ² , not significant [NS]), while a small, but significant, overestimation was seen for the MDRD formula (+3.43 mL/min/1.73 m ² , p = 0.003). Precision and accuracies within 50% of true GFR (93.1% and 88.2%, respectively) tended to be higher for the BTP formula, but the differences did not reach significance. The White equation overestimated the true GFR by 9.43 mL/min/1.73 m ² (p = 0.001), and was inferior with respect to precision and 50% accuracy (79.4%). BTP-based GFR calculations are reliable, and may serve as an alternative to the re-expressed MDRD equation .     

Hyperlipidemia Is Associated With Accelerated Chronic Kidney Disease Progression After Lung Transplantation

Hyperlipidemia is associated with faster progression of chronic kidney disease (CKD) in the general public. We sought to investigate this association after lung transplantation. Data was retrospectively collected on 230 lung recipients transplanted between January 1997 and December 2003. Estimated glomerular filtration rates (eGFR) and lipid levels were recorded at regular intervals posttransplant. Independent associations between lipid levels early posttransplant and pertinent renal endpoints were investigated. Baseline LDL was 110 ± 35 mg/dL and remained unchanged at 6 months. A faster decline in eGFR was seen in those with 6 month LDLs > versus < the mean level of 110 mg/dL (p = 0.05). By 6 months posttransplant eGFRs were lower in the 6 month LDL > versus < 110 mg/dL group (53 ± 23 vs. 62 ± 29 mL/min/1.73 m², p = 0.01), a difference that persisted at 60 months (39 ± 24 vs. 73 ± 57 mL/min/1.73 m², p = 0.05). On univariate analysis, a 6 month LDL in the highest quartile, i.e. >140 mg/dL, predicted faster progression to CKD, defined as declining to an eGFR < 30 mL/min/1.73 m² (HR 1.5, p = 0.01). This finding persisted in the multivariate Cox-proportional model (HR 1.4, p = 0.02). Hyperlipidemia predicts faster decline in renal function after lung transplant. Prospective trials are needed to confirm this finding.     

Validation of plasma clearance of 51Cr-EDTA in adult renal transplant recipients: comparison with inulin renal clearance

Plasma clearance of ⁵¹Cr-EDTA (⁵¹Cr-EDTA-Cl) is an alternative method to evaluate glomerular filtration rate (GFR). This study aimed to investigate the concordance between ⁵¹Cr-EDTA-Cl and renal inulin clearance (In-Cl) in renal transplant recipients as well to determine the repeatability of ⁵¹Cr-EDTA-Cl in kidney donors. Forty four kidney recipients and 22 kidney donors were enrolled. Simultaneous measurements of ⁵¹Cr-EDTA-Cl and In-Cl were performed. A single dose of 3.7MBq of ⁵¹Cr-EDTA was injected and the plasma disappearance curve was created by taking blood samples at 2, 4, 6 and 8 h after injection. Bland and Altman statistical approach was used to quantify the agreement between In-Cl and ⁵¹Cr-EDTA-Cl and to determine the better concordance between all possibilities of measure for the ⁵¹Cr-EDTA-Cl. The mean of In-Cl was 44.5 ± 17.9 ml/min/1.73 m². There was a positive correlation between In-Cl and all possible measurements of ⁵¹Cr-EDTA-Cl. ⁵¹Cr-EDTA-Cl with two samples taken at 4 and 8 h or at 4 and 6 h presenting the narrow limits of agreement and a difference (bias) of 2.8 and 2.7 ml/min, respectively. Two plasma sampling for ⁵¹Cr-EDTA-Cl was a reliable method to measure GFR compared with In-Cl and comprises a suitable method to be used in kidney transplanted patients.     

Rapid Decline in 51Cr-EDTA Measured Renal Function During the First Weeks Following Lung Transplantation

We previously described a 54% decline in renal function at 6 months after lung transplantation (LTx). We hypothesized that this decline is a very early event following LTx.
Thirty-one consecutive patients (16 females/15 males), mean age 49 (±13) years, with emphysema, cystic fibrosis/bronchiectasis or idiopathic pulmonary fibrosis were included in an analysis of renal function before and after LTx. The glomerular filtration rate (GFR) was measured using the ⁵¹Cr-ethylenediaminetetra acetic acid plasma clearance single injection technique (mGFR) at baseline before transplantation and at 1, 2, 3 and 12 weeks postoperatively.
Mean mGFR declined from 103 ± 18 to 65 ± 22, 53 ± 16 and 57 ± 18 mL/min/1.73m² at 1-, 3- and 12-weeks post-LTx (p < 0.0001), respectively. In a time-dependent repeated measures ANOVA, risk factors for a decline in mGFR posttransplant included: time (p < 0.0001), acute renal failure within 2 weeks post-LTx (p = 0.0003), use of heart and lung machine (p = 0.04), and the use of ephedrine (p = 0.048), as well as increasing age, older than 18 years at LTx (p = 0.006). These data demonstrate that renal function, measured with an isotope method, decreases dramatically during the first week after LTx.     

A Randomized, Multicenter Study of Steroid Avoidance, Early Steroid Withdrawal or Standard Steroid Therapy in Kidney Transplant Recipients

In a randomized, open-label, multicenter study, de novo renal transplant patients received no steroids (n = 112), steroids to day 7 (n = 115), or standard steroids (n = 109) with cyclosporine microemulsion (CsA-ME), enteric-coated mycophenolate sodium (EC-MPS) and basiliximab. The primary objective, to demonstrate noninferiority of 12-month GFR in the steroid-free or steroid-withdrawal groups versus standard steroids, was not met in the intent-to-treat population. However, investigational groups were not inferior to standard steroids in the observed-case analysis. Median 12-month GFR was not significantly different in the steroid-free or steroid-withdrawal groups (58.6 mL/min/1.73 m² and 59.1 mL/min/1.73 m²) versus standard steroids (60.8 mL/min/1.73 m²). The 12-month incidence of biopsy-proven acute rejection (BPAR), graft loss or death was 36.0% in the steroid-free group (p = 0.007 vs. standard steroids), 29.6% with steroid withdrawal (N.S.) and 19.3% with standard steroids. BPAR was significantly less frequent with standard steroids than either of the other two regimens. Reduced de novo use of antidiabetic and lipid-lowering medication, triglycerides and weight gain were observed in one or both steroid-minimization group versus standard steroids. For standard-risk renal transplant patients receiving CsA-ME, EC-MPS and basiliximab, steroid withdrawal by the end of week 1 achieves similar 1-year renal function to a standard-steroids regimen, and may be more desirable than complete steroid avoidance.     

L- carnitine in idiopathic asthenozoospermia: a multicenter study

Summary. The aim of the study described here was to evaluate any possible effect of L-carnitine on spermatozoal motility in a group of patients with unexplained asthenozoospermia in four different infertility centres. One hundred patients received 3 g d⁻¹ of oral L-carnitine for 4 months. Sperm parameters were studied before, during and after this treatment. Motility was also studied by means of a computer-assisted sperm analysis.
The results of the study indicate that L-carnitine is able to increase spermatozoal motility, both in a quantitative and in a qualitative manner (per cent motile spermatozoa increased from 26.9±1.1% to 37.7 ± 1.1% [ P < 0.001]; per cent spermatozoa with rapid linear progression increased from 10.8 ± 0.6% to 18.0 ± 0.9% [ P < 0.001]; mean velocity increased from 28.4 ± 0.6 μm s⁻¹ to 32.5 ± 0.8 μm s⁻¹ [ P < 0.001]; linearity index increased from 3.7 ± 0.1 to 4.1±0.1 [ P < 0.001], especially in the subgroup of patients with poor rapid linear progression of spermatozoa (per cent of motile spermatozoa increased from 19.3± 1.9% to 40.9± 1.4% [ P < 0.001], and per cent of spermatozoa with rapid linear progression increased from 3.1±0.4% to 20.3±1.6% [ P < 0.001]) An increase in spermatozoal output was also observed (total number of ejaculated spermatozoa increased from 142.4 ± 10.3 10⁶ to 163.3 ± 11.0 × 10⁶ [ P < 0.001]). The authors conclude that oral administration of L-carnitine may improve sperm quality at least in patients with idiopathic asthenozoospermia.     

Twenty-Year Experience With Heart Transplantation for Infants and Children With Restrictive Cardiomyopathy: 1986–2006

Idiopathic restrictive cardiomyopathy (RCM) is a rare cardiomyopathy in children notable for severe diastolic dysfunction and progressive elevation of pulmonary vascular resistance (PVR). Traditionally, those with pulmonary vascular resistance indices (PVRI) >6 W.U. × m² have been precluded from heart transplantation (HTX). The clinical course of all patients transplanted for RCM between 1986 and 2006 were reviewed. Preoperative, intraoperative and postoperative variables were evaluated. A total of 23 patients underwent HTX for RCM, with a mean age of 8.8 ± 5.6 years and a mean time from listing to HTX of 43 ± 60 days. Preoperative and postoperative (114 ± 40 days) PVRI were 5.9 ± 4.4 and 2.9 ± 1.5 W.U. × m², respectively. At time of most recent follow-up (mean = 5.7 ± 4.6 years), the mean PVRI was 2.0 ± 1.0 W.U. × m². Increasing preoperative mean pulmonary artery pressure (PA) pressure (p = 0.04) and PVRI > 6 W.U. × m² (χ²= 7.4, p < 0.01) were associated with the requirement of ECMO postoperatively. Neither PVRI nor mean PA pressure was associated with posttransplant mortality; 30-day and 1-year actuarial survivals were 96% and 86%, respectively. Five of the seven patients with preoperative PVRI > 6 W.U. × m² survived the first postoperative year. We report excellent survival for patients undergoing HTX for RCM despite the high proportion of high-risk patients.     

Gonadal and Extragonadal Sperm Reserves of the Brazilian Nelore Zebu (Bos indicus)

Summary: Gonadal and extragonadal sperm reserves were estimated through hemocytometric method in six Nelore zebu bulls, aging 4–6 years, with normal spermatogenesis, and kept at sexual rest. Gonadal sperm reserve was estimated to be 47.8 ± 5.8 times 10⁶ sperm cells/g testis parenchyma and 9.8 ± 1.7 times 10⁹ sperm cells/testis. Using a time divisor of 4.94 days the daily sperm production was estimated to be 10.0 ± 0.9 times 10⁶ sperm cells/g testis parenchyma/day and 2.0 ± 0.3 times 10⁹ sperm cells/testis/day. Epididymal sperm reserve amounted 11.9 ± 1.6 times 10⁹ spermatozoa/organ, distributed as follows: 35.3 ± 3.6% in the head, 16.9 ± 1.7% in the body and 47.7 ± 3.7% in the tail.
Zusammenfassung: Gonadale und extragonadale Spermareserven des brasilianischen Nelore-Zebu (Bos indicus)
Bei sechs Nelore-Zebubullen im Alter von vier bis sechs Jahren mit normaler Spermatogenese und unter sexueller Karenz wurden mit einer haemocytometrischen Methode die gonadalen und extragonadalen Spermareserven bestimmt. Für die gonadale Spermareserve wurden Werte von 47.8 ± 5.8 times 10⁶ Spermatozoen/g Hodenparenchym und 9.8 ± 1.7 times 10⁹ Spermatozoen/Hoden gefunden. Unter Benutzung eines Zeitdivisors von 4.94 Tagen berechnet sich die tägliche Spermaproduktion zu 10.0 ± 0.9 times 10⁶ Spermatozoen/g Hodenparenchym/Tag und 2.0 ± 0.3 times 10⁹ Spermatozoen/Hoden/Tag. Die Spermareserve im Nebenhoden betrug 11.9 ± 1.6 times 10⁹ Spermatozoen/Nebenhoden in folgender Verteilung: 35.3 ± 3.6% im Nebenhodenkopf, 16.9 ± 1.7% im Nebenhodenkörper und 47.7 ± 3.7% im Nebenhodenschwanz.     

Kidney transplantation in patients with Fabry disease

Little is known about the effects of enzyme replacement therapy (ERT) in kidney transplant recipients with Fabry disease. Clinical characteristics of transplant recipients in the Fabry Outcome Survey (FOS) were therefore examined in patients with Fabry disease with or without ERT. Of the 837 European patients in FOS (March 2006), 34 male patients and two female patients had received kidney transplants. Mean age at transplantation was 37.6 ± 10.9 years, mean time since transplantation was 7.7 ± 6.4 years, median estimated glomerular filtration rate (eGFR) was 44.4 ml/min/1.73 m², and median proteinuria was 296 mg/24 h. Of 27 patients with baseline data, 59% had hypertension, 74% had left ventricular hypertrophy, 22% had cardiac valve disease, 30% had arrhythmia, and 22% had transient ischaemic attacks and 15% stroke. Twenty patients (74%; two female patients, 18 male patients) were receiving ERT with agalsidase alfa. At enrolment or at the start of ERT, median eGFRs were 59 and 35 ml/min/1.73 m² ( P  = 0.05) and median proteinuria levels were 240 and 420 mg/24 h (not significant) in treated and untreated patients respectively. Renal function remained stable in patients receiving ERT. In conclusion, agalsidase alfa is well tolerated in patients with Fabry disease who have undergone renal transplantation.     

Pharmacokinetics and Placental Transmission of Fazadinium in Elective Caesarean Sections

The pharmacokinetics and placental transmission of fazadinium (0.75-0.80 mg kg^-1) were studied in seven pregnant women undergoing elective caesarean section. Plasma levels of the drug were determined by a spectrofluorimetric method and pharmacokinetics were derived according to a 2-compartment open model. Distribution and elimination half-lives averaged 0.07 ±0.03 (t½alpha) and 1.24 ± 0.34 (t½ beta) h; the volume of distribution was 20.75± 5.81 1, and the plasma clearance was 202.33 ± 39.2 ml min^-1 1.73 m². The ratio between umbilical venous blood and maternal blood at delivery ranged from 2.57 to 17.5%. Urinary elimination accounted for 37% of the injected dose within 24 h. It is concluded that because of early good intubating conditions and favourable pharmacokinetics with a modest placental passage, fazadinium might be particularly useful in obstetrics.     

Correlation of Nuclear Morphometry and Immunostaining for p53 and Proliferating Cell Nuclear Antigen in Transitional Cell Carcinoma of the Bladder

Background :
In an attempt to determine the biological significance of nuclear morphometric findings, measurements of mean nuclear volume (MNV) and nuclear roundness factor (NRF) were compared to the immunoreactivityof p53 expression and proliferating cell nuclear antigen (PCNA) in human bladder cancer.
Methods :
MNV and NRF were measured using stereological methods. Expression of p53 and PCNA were determined by immunohistochemical staining. Specimens from 111 patients with previously untreated bladder cancer were analyzed.
Results :
The mean MNV was 235.8 ± 1 33.6 μm³ for the 81 patients with p53-labeling index (LI) less than 10% and 337.2 ± 141.0 μn³ for the 30 patients with p53 LI greater than 10% (P = 0.008). There was Resign if icant correlation between NRF and expression of p53. The mean MNV was 220.1 ± 1 20.5 μm³ for the 67 patients with PCNA LI less than 28% (the mean value of PCNA LI) and 328.9 ± 149.2 μm³ in 44 patients with PCNA LI greater than 28% (P= 0.0001). The mean NRF was 80.7 ± 4.2 for the 67 patients with PCNA LI less than 28%, and 82.3 ± 3.4 for the 44 patients with PCNA LI more than 28% (P= 0.04). Conclusion: Nuclear morphometric findings may reflect the proliferative potential of cancer eel Is of the bladder, as indicated by findings of immunostaining for p53 and PCNA.     

Hemodynamic and Cardiometabolic Effects of Prenalterol in Patients with Gram Negative Septic Shock

The hernodynamic eflects of prenalterol, a new inotropic agent, were investigated in 10 patients with gram negative septic shock. In four of the patients, coronary sinus blood flow (CSF) and myocardial oxygen and lactate extraction were also determined. After baseline hemodynamic measurements, prenalterol was infused intravenously over a 10-min period to a total dose of 150 pg/kg. All patients responded within 15 min after completion of prenalterol infusion by increasing mean arterial pressure from 57±11 to 75 ± 20 mmHg (7.58f 1.46 to 9.97±2.66 kPa), (+32%), ( P<0.01 ) and cardiac index from 2.65±0.40 to 3.80±0.47 l min^-l m^-2 (+44%) ( P < 0.001). There was no change in heart rate or systemic vascular resistance, nor were any arrhythmias recorded. The urinary output increased significantly. After prenalterol, CSF increased from 185kl 4 to 246±14 ml.min-¹, (+33%), (P<0.001) and myocardial oxygen and lactate extraction rose from 19.8±2.1to26.6±2.1 ml O₂.min^-1, (+ 34%) (P<0.00l) andfrom33.2±2.3 to44.7k2.1 μmol.min^-1, (+35%), (P<0.001), respectively. The total body oxygen consumption increased from 287f 13 to 348±23 ml O₂.min^-1, (+21 %), ( P<0.01 ) and the arterial lactate concentration decreased from 5.61±0.55 to 3.94±0. 16 mmol.l^-1, (- 30%), (P<0.01), suggesting improved tissue perfusion. The results demonstrate that prenalterol is a potent, highly selective inotropic agent inducing the same magnitude of increase in blood pressure and cardiac output as reported for dopamine in septic shock.     

Tumor-infiltrating lymphocytes derived from human renal cell carcinoma: Clonal analysis of its characteristics

Aim:   To assess the characteristics of activated tumor-infiltrating lymphocytes (TIL), we report the isolation, growth response, and functional analysis of a CD4^- CD8⁺ TIL-clone derived from human renal cell carcinoma (RCC).
Methods:   Bulk TILs were expanded from a human RCC and the lymphocytes were separated into a CD8⁺ enriched population. Subsequently, using the limiting dilution technique, a TIL clone was established and its growth response, phenotype and cytotoxic activity were analyzed.
Results:   A clone, T16-13, by day 94 numbering 1 × 10⁷ cells, was harvested and characterized as a CD4^- CD8⁺ clone. On day 144, the cytotoxic activity of this clone against the autologous tumor was relatively high (2.3 ± 0.7 LU₃₀/10⁶ cells). Meanwhile, against allogeneic renal tumors, there was no cytotoxic activity (−0.1 LU₃₀/10⁶ cells).
Conclusions:   A TIL clone possessing modest autologous tumor-specific cytotoxicity can be isolated from human RCC. The characteristics analysis of various TIL clones may provide a better understanding of an RCC tumor microenvironment and may help to establish new modalities for the treatment of patients with metastatic kidney cancer.     

Intrathoracic and pulmonary blood volume during CO2-pneumoperitoneum in humans

Background : Induction of CO₂-pneumoperitoneum may have significant effects on systemic and pulmonary haemodynamics. We hypothesized, that intrathoracic (ITBV) and pulmonary blood volume (PBV) are affected during intra-abdominal CO₂-insufflation, which may be pronounced by positional changes of the patient.
Methods : Sixteen anaesthetized patients were studied before, during and after CO₂-pneumoperitoneum for laparoscopic cholecystectomy. A dye indicator technique was used to assess ITBV and PBV. In addition, gas exchange and haemodynamics were recorded.
Results : In the supine position, induction of CO₂-pneumoperitoneum had no effects on ITBV, PBV and cardiac output. Mean systemic arterial pressure increased from 10.9±1.5 kPa (82±11 mmHg) to 12.7±1.5 kPa (95±11 mmHg, P<0.01). In the reverse Trendelenburg position ITBV decreased from 19.8±5.1 ml . kg^-1 to 16.7±3.7 ml . kg¹ ( P <0.05) during CO₂-insufflation, but increased to control values after 20 min. PBV decreased from 4.2±1.2 ml . kg^-1 to 3.4±1.1 ml . kg^-1 (P<0.05) and remained decreased during CO₂-pneumoperitoneum. Calculated venous admixture was unchanged throughout the study. Deflation of CO₂-pneumoperitoneum increased ITBV (22.4±5.2 ml . kg^-1, P<0.05) and cardiac output above control values.
Conclusions : In anaesthetized-paralyzed patients in the reverse Trendelenburg position intra-abdominal CO₂-insufflation is associated with significant alterations of ITBV and PBV. The release of CO₂-pneumoperitoneum is associated with a re-distribution of blood into the thorax.     

Long-term renal allograft function under maintenance immunosuppression with cyclosporin A or azathioprine: A single center, five-year follow-up study

Abstract. In order to evaluate long-term renal graft function, 149 cyclosporin A and prednisolone (CyA/P)-treated renal transplant recipients were compared with 119 azathioprine and prednisolone (Aza/P)-treated patients. Only patients who had a functioning graft for at least 1 year and who were maintained on their initial immunosuppressive protocol were included. The minimum follow-up period was 4 years. Renal graft function was estimated by yearly determinations of serum creatinine and creatinine clearance. The CyA/P-treated patients had a significantly higher serum creatinine and a significantly lower creatinine clearance at every point in time post-transplantation than Aza/P-treated patients ( P < 0.001). The evolution of renal graft function, as reflected in the line of regression for serum creatinine and creatinine clearance versus time, was estimated for each individual patient. There was an almost stable renal function, as assessed by the median of the slopes of the regression line for serum creatinine versus time in both groups. The median increase in serum creatinine was only 1.4 μmol/l per year for Aza/P-treated patients and 2.4 μmol/l per year for CyA/P-treated patients (difference NS). The median decline in creatinine clearance was 2.18 ml/min per 1.73 m²/year in the Aza/P group and 1.07 ml/min per 1.73 m²/year in the CyA/P group ( P = 0.05). In patients with a functioning graft for at least 5 years, creatinine clearance remained unchanged in both groups during the study period. In conclusion, renal graft function, as assessed by measurements of serum creatinine and creatinine clearance, remained essentially unchanged for at least 5 years after transplantation, regardless of the immunosuppressive protocol used. Thus, these data do not indicate a progression with time of the nephrotoxicity observed in CyA-treated patients.     

Effects of ultraviolet B irradiation on fetal pig islet-like cell clusters

Abstract: Ultraviolet B (UV-B) irradiation of donor islets has previously been shown to result in the prolongation of their survival when transplanted into rodents. This study examined the in vitro and in vivo effects of UV-B irradiation on fetal pig islet-like cell clusters (ICCs), which like adult islets are being transplanted to reverse diabetes. Under control conditions, fetal pig ICCs were able to stimulate both human and pig peripheral blood mononuclear cells (PBMC) in mixed islet lymphocyte culture (MILC). Exposure of the ICCs to UV-B irradiation significantly reduced their ability to stimulate PBMC of both species in MILC when 600 J/m² but not lower doses (300 and 400 J/m²) of irradiation were applied. In contrast, all doses of UV-B irradiation were effective in inhibiting the ability of pig and human PBMC to stimulate human PBMC in a mixed lymphocytes culture (MLC). This demonstrates that UV-B irradiation is effective in reducing xeno immunogenicity of pig antigens. A toxic effect of all doses of UV-B irradiation on ICCs was demonstrated in vitro with a reduction in ³H-thymidine incorporation of 57, 71, 64, and 80% at 150, 300, 450, and 600 J/m², respectively. Toxicity of UV-B irradiation was also demonstrated when treated ICCs were transplanted beneath the renal capsule of SCID mice. The insulin content of the ICCs, 6 weeks after transplantation, was significantly reduced in the 600 J/m² group ( P <0.05). ICCs treated with UV-B irradiation (300 J/m²) in vitro and then transplanted beneath the renal capsule of BALB/c mice were rejected within 2 weeks as were untreated ICCs. Injection of cyclosporine (12.5 mg/kg/day) into these mice did not alter the results. It is concluded that UV-B irradiation is toxic to fetal pig ICCs and, in low dose, unable to prevent their rejection when transplanted into mice.     

The Effect of Surgical Stress on Haemodynamics During Neurolept Anaesthesia

The influence of surgical stress on haemodynamics during neurolept anaesthesia (NLA) was studied in ten patients, while they were awake, under anaesthesia prior to surgery and peroperatively. Systemic arterial, pulmonary arterial, right atrial and pulmonary capillary wedge pressures, as well as cardiac output (Q_t), arterial oxygen content and mixed venous oxygen content, were measured. Systemic and pulmonary vascular resistances, arterial-venous oxygen content difference (AVD), oxygen consumption (v_o2 and cardiac index (CI) were calculated.
On institution of anaesthesia, CI fell from 2.8 ±.11 /min. m² to 2.5±0.2 l /min.m² and systolic arterial pressure (SBP) fell from 13.4±0.5 kPa to 10.2±0.3 kPa. During surgery CI rose to 3.3±0.1 1/min.m² and SBP rose to 15.7±0.6 kPa. Prior to anaesthesia, AVD was 40.2±0.2 ml/l Under anaesthesia prior to surgery, AVD did not change, but v_O2 declined from 207±13 ml/min to 171±10 ml/min. During surgery, AVD fell to 30.5±0.3 ml/l, while V_o2 remained unchanged.
It is concluded that NLA has a direct metabolic depressant effect and, in association with surgery, is accompanied by hyperkinetic circulation.