Renal complications following lung and heart-lung transplantation

As survival improves after lung and heart-lung transplants, the long term detrimental impact of current management on renal function becomes more apparent as the number of non-renal solid organ transplant recipients on renal transplant waiting lists increases. Progressive chronic kidney disease (CKD) is a significant cause of morbidity and mortality in the transplant population. In this review we discuss the specific problems prior to lung or heart-lung transplant that predispose to CKD, as well as potential renal complications encountered during the peri- and post-transplant period. Significant acute and chronic nephrotoxicity is caused by calcineurin inhibitors (CNI). Mechanisms to decrease CNI exposure exist but have yet to be adopted in routine clinical care. Modifiable risk factors and the current screening and management approach taken at our institution are described. Pediatric nephrologists should be involved from an early stage. Future work will need to focus on identifying more accurate measures of renal function, given the limitations of current glomerular filtration rate estimation equations in a population where nutritional status may rapidly change post transplant. Multicentre studies of CNI minimisation strategies are required to guide future therapy that aims to minimise CKD development and progression in this vulnerable population.     

A comparison of the side effects of prilocaine with felypressin and lignocaine with adrenaline in large loop excision of the transformation zone of the cervix: results of a randomised trial

Objective To test the hypothesis that prilocaine with felypressin causes fewer side effects than lignocaine with adrenaline when performing large loop excision of the transformation zone of the cervix.
Design Randomised trial.
Setting Colposcopy clinic in a large district general hospital.
Participants Two hundred consecutive women undergoing large loop excision of the transformation zone of the cervix.
Methods Two different local anaesthetic combinations (prilocaine with felypressin and lignocaine with adrenaline) were compared in women undergoing large loop excision of the transformation zone. Prospective collection of clinical and treatment data was undertaken with scoring using an ordinal scale of pain experienced by the women during the procedure. Peri-operative blood loss and any side effects were also recorded.
Main outcome measures Side effects associated with the local anaesthetic agents.
Results Lignocaine with adrenaline resulted in less blood loss (   P = 0.006  ) but was more likely to cause side effects, such as feeling faint (   P = 0.017  ) and shaking (   P < 0.001  ).
Conclusion Prilocaine with felypressin causes fewer side effects than lignocaine with adrenaline and is therefore the preferred local anaesthetic combination for large loop excision of the transformation zone.     

Epstein-Barr virus monitoring in paediatric renal transplant recipients

Prospective Epstein-Barr virus (EBV) surveillance post transplant was undertaken by qualitative polymerase chain reaction testing for EBV DNA in plasma so as to detect EBV viremia as early as possible and thereby attempt to pre-empt post-transplant lymphoproliferative disease by reduction of immunosuppression. Forty-three children (46 transplants) were followed for a median (range) of 15.5 (3-25) months. Thirty-one children (67%) were EBV seropositive pre transplant. Twenty children (44%) developed EBV viremia; of these 9 (60%) were seronegative and 11 (36%) seropositive recipients. Primary infection developed later (median difference 14.2 weeks, P=0.009), was more likely to be symptomatic (odds ratio 2.91, 95% confidence interval 0.95-4.88) and associated with a rise in serum creatinine (odds ratio 6.13, 95% confidence interval 4.13-8.13) than reactivation disease. There was a higher incidence of EBV disease in children receiving quadruple therapy and tacrolimus (odds ratio 13.2, 95% confidence interval 11.5-14.9) compared with those given cyclosporin-based immunosuppression. Immunosuppression was reduced when EBV infection was detected. All children became asymptomatic and renal function returned to normal by a median (range) of 17 (6-52) days, although mild relapses occurred in 3 children. Regular EBV surveillance allowed prompt reduction of immunosuppression and was associated with a good outcome in this group of children.     

High-pressure liquid chromatographic analysis of triflubazam and its metabolites in human and animal blood and urine.

A high-pressure liquid chromatographic method is described for analyzing triflubazam [1-methyl-5-phenyl-7-trifluoromethyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione] and its primary metabolites in blood and urine. Adsorption chromatography, using pellicular silica gel as the stationary phase and dioxane-isooctane as the mobile phase, permitted rapid sample analysis. After extraction of blood and urine samples with toluene, quantitation is achieved using liquid chromatography with an internal standard. The method is sensitive above 50 ng/ml of triflubazam and its known metabolites. Recoveries for all compounds from blood or urine averaged above 95 percent. The specificity of the method was established by collecting samples separated by liquid chromatography and characterizing them by mass spectrometry. Human and animal data are presented to illustrate the utility of the method.     

Cardiovascular changes in preeclampsia

The cardiovascular system undergoes a host of changes in association with the development of preeclampsia, which ultimately lead to the classic low cardiac output-high systemic vascular resistant state. A newer hypothesis suggests that exaggeration of the normal for pregnancy hyperdynamic, low-resistance state commencing in early gestation is responsible for the genesis of the clinically apparent vasoconstrictive disease in late pregnancy. Such events may also lead to the vascular damage that persists into later life. In preeclampsia, cardiac contractility is preserved but both steady and pulsatile arterial load are increased inappropriately, failing to decrease as would occur in normal pregnancy, involving both conduit and small vessels. Abnormal adaptive mechanisms may be secondary to changes in vascular tone or vascular wall elements, and may have future implications for a woman later in life.     

Somatostatin and gamma-aminobutyric acid inhibit interleukin-1 beta-stimulated release of interleukin-6 from rat C6 glioma cells

OBJECTIVE: We investigated the ability of inhibitory neurotransmitters to alter the interleukin-1 beta (IL-1 beta)-stimulated release of interleukin-6 (IL-6) from cultured glial tumor cells. METHODS: C6 rat glioblastoma cells were exposed to either IL-1 beta or its putative second messenger lysophosphatidylcholine (LPC) in the absence or presence of the inhibitory neurotransmitters somatostatin (SRIF) or gamma-aminobutyric acid (GABA). Alternatively, C6 cells were pretreated with selective inhibitors of JNK or p38 and then exposed to either IL-1 beta or LPC to determine the relative involvement of these terminal stress kinases in the stimulation of IL-6 release. RESULTS: IL-1 beta promoted the release of IL-6 with a maximally effective concentration of 25 ng/ml. Both SRIF-14 and SRIF-28 comparably suppressed stimulated IL-6 release with an ED(50) of approximately 50 nM. GABA also prevented IL-1 beta-driven IL-6 release (ED(50) = 100 microM). IL-1 beta and LPC synergistically enhanced release of IL-6 in the presence of the beta-adrenergic receptor agonist isoproterenol (ISO); these effects were largely reversed by SRIF or GABA. The pyridinylimidazole inhibitor of p38, SB-203580, completely blocked stimulation of IL-6 release by IL-1 beta or LPC; conversely, the anthrapyrazolone JNK inhibitor, SP-600125, was ineffective in modifying stimulated IL-6 release. CONCLUSIONS: The effects of IL-1 beta and LPC on IL-6 release from glioma cells are effectively antagonized by the inhibitory neurotransmitters SRIF and GABA. On the basis of correlative studies, we propose that the ability of inhibitory transmitters such as SRIF and GABA to counter the induction of IL-6 release may entail suppression of p38 activity.