Combined liver–kidney and liver transplantation in patients with renal failure outcomes in the MELD era

With the implementation of the Model for End-Stage Liver Disease (MELD) scoring system, the number of combined liver–kidney transplants (CLKT) has increased dramatically. The United Network for Organ Sharing (UNOS) dataset was analysed for adult recipients with renal failure for the period between February 2002 and April 2006. This group was subdivided into patients on hemodialysis (HD) and to those not on HD prior to transplantation. All recipients in renal failure (serum creatinine ≥2.5 mg/dl) at the time of transplantation were included. A total of 1397 subjects were in renal failure but not on HD (18% received a CLKT, 82% underwent LT alone). Another 1740 subjects were on HD prior to transplantation (41% received a CLKT while 59% received a LT). In dialysis-dependent recipients, Cox regression analysis demonstrated CLKT had an independent protective effect. In subjects on HD, CLKT had improved survival at 1 year (79.4 vs. 73.7%, P  = 0.004). In patients in renal failure without HD, CLKT was not protective.  CLKT subjects had a nonsignificant difference in survival as compared with patients who had undergone liver transplantation alone, at 1 year (81.0% vs. 78.8%, P  > 0.10). In subjects undergoing CLKT, there was improved survival at 1 year as compared with LT-alone patients on hemodialysis; however, in patients with renal failure, but not on hemodialysis, there was no difference in survival when comparing CLKT to LT-alone.     

Urethral Venous Malformation: An Unusual Cause of Recurrent Post-Coital Gross Haematuria in Association with Haematospermia

Three cases of recurrent post-coital haematuria are described. Extensive protracted investigations pinpointed urethral varicosities as the likely cause. All patients were successfully treated with diathermy fulguration.     

Use of the H3 receptor antagonist radioligand [3H]-A-349821 to reveal in vivo receptor occupancy of cognition enhancing H3 receptor antagonists

Background and purpose:

The histamine H₃ receptor antagonist radioligand [³H]-A-349821 was characterized as a radiotracer for assessing in vivo receptor occupancy by H₃ receptor antagonists that affect behaviour. This model was established as an alternative to ex vivo binding methods, for relating antagonist H₃ receptor occupancy to blood levels and efficacy in preclinical models.

Experimental approach:

In vivo cerebral cortical H₃ receptor occupancy by [³H]-A-349821 was determined in rats from differences in [³H]-A-349821 levels in the isolated cortex and cerebellum, a brain region with low levels of H₃ receptors. Comparisons were made to relate antagonist H₃ receptor occupancy to blood levels and efficacy in a preclinical model of cognition, the five-trial inhibitory avoidance response in rat pups.

Key results:

In adult rats, [³H]-A-349821, 1.5 µg·kg⁻¹, penetrated into the brain and cleared more rapidly from cerebellum than cortex; optimally, [³H]-A-349821 levels were twofold higher in the latter. With increasing [³H]-A-349821 doses, cortical H₃ receptor occupancy was saturable with a binding capacity consistent with in vitro binding in cortex membranes. In studies using tracer [³H]-A-349821 doses, ABT-239 and other H₃ receptor antagonists inhibited H₃ receptor occupancy by [³H]-A-349821 in a dose-dependent manner. Blood levels of the antagonists corresponding to H₃ receptor occupancy were consistent with blood levels associated with efficacy in the five-trial inhibitory avoidance response.

Conclusions and implications:

When employed as an occupancy radiotracer, [³H]-A-349821 provided valid measurements of in vivo H₃ receptor occupancy, which may be helpful in guiding and interpreting clinical studies of H₃ receptor antagonists.     

Internal jugular phlebectasia as an incidental finding in cervical spine surgery

Idiopathic internal jugular phlebectasia, occurs either unilaterally or bilaterally affecting the internal jugular vein is a rare congenital variation often diagnosed during childhood. It usually presents with a benign swelling over the lateral side of neck on the affected side, seen on exertion. A-30-year old male was operated for anterior cervical dissectomy from right lateral approach and was diagnosed per-operatively as internal jugular phlebectasia. The surgery was abandoned at this stage on the advice of cardiothoracic surgeon to investigate the patient for the secondary etiological factors for internal jugular vein dilatation. The patient was reassured without any active intervention for the phlebectasia and cervical dissectomy was performed in the second surgery through the lateral approach from left side. This case is presented in view of rarity and suggested that during preoperative workup the nearby structures like carotid sheath should be evaluated by magnetic resonance imaging to avoid such per-operative surprises.     

Long-term follow-up of very old heart failure patients enrolled in a trial of exercise training

Little is known about how physical and psychological status changes with time in older heart failure patients. The authors followed up a cohort of 82 patients (mean age, 80.5 years) enrolled in a randomized controlled trial of exercise training in heart failure. Six-minute walk test, accelerometry, functional status, quality of life, anxiety, and depression were measured at baseline, 3 months, 6 months, and a mean of 19 months post-enrollment. There were no significant differences between the exercise and control groups at long-term follow-up. Six-minute walk distance declined by only 0.2 m/month in those attending final follow-up (vs 4.6 m/month in nonattenders; P=.03). Similar results were seen for other outcomes. Only a small proportion of the variance in change of any of the outcomes was explained by differences in baseline variables.     

Visual attention in children with migraine: a controlled comparative study

The aim of this study was to evaluate the visual attention of children with migraine and compare it with a control group. Thirty migrainous children and 30 controls without headache were subjected to a visual attention assessment with Trail Making Tests (TMT) A/B, Letter Cancellation Test, and the Brazilian computerized test Visual Attention Test, third edition. The migraine group was evaluated after 2 days without headache. The migraine group had an inferior performance compared with the control group on TMT A ( P  = 0.03) and B ( P  = 0.001), and more errors on tasks 1 ( P  = 0.032) and 2 ( P  = 0.015) of the Visual Attention Test, presenting difficulty with selective and alternate attention. Attention is a neurological function that depends on structures such as the brainstem, cerebral cortex and the limbic system and on neurotransmitters such as dopamine and noradrenaline. The neurochemical aspects involved in the physiopathology of migraine and attention mechanisms probably predispose these children to visual attention deficits.     

Comparison of pulmonary and pleural responses of rats and hamsters to inhaled refractory ceramic fibers

The present study was designed to determine whether pleural fiber burdens or subchronic pleural fibroproliferative and inflammatory changes can help explain the marked interspecies differences in pleural fibrosis and mesothelioma that are observed following long-term inhalation of RCF-1 ceramic fibers by rats and hamsters. Fischer 344 rats and Syrian golden hamsters were exposed to RCF-1 for 4 h per day, 5 days per week, for 12 consecutive weeks. Lung and pleural fiber burdens were characterized during and after exposure. For all time points, approximately 67% of fibers associated with lung tissues from both rats and hamsters were longer than 5 microns in length. In comparison, fibers longer than 5 microns recovered from the pleural compartment, following a 12-week exposure and 12 weeks of recovery, accounted for 13% (hamsters) and 4% (rats) of the distribution. In the 12 weeks after the cessation of exposure, the number of fibers longer than 5 microns in length remained constant in the hamster at approximately 150 fibers per cm2 pleura. This was 2 to 3 times the corresponding fiber surface density in the rat. Significant pulmonary and pleural inflammation was detected at all time points and for both species. DNA synthesis by pleural mesothelial cells was quantified by bromodeoxyuridine uptake following 3 days of labeling. Labeling indices were higher in hamsters than in rats, both for RCF-1-exposed and filtered air-control animals and was highest for the parietal surface of the pleura. Significantly greater collagen deposition was measured in the visceral pleura of hamsters 12 weeks post-exposure but was not significantly elevated in rats. These findings demonstrate that subchronic inhalation exposure to RCF-1 induces pleural inflammation, mesothelial-cell turnover, pleural fibrosis, and an accumulation of fibers with a length greater than 5 microns in the hamster. The accumulation of long fibers in the pleural space may contribute to the pathology observed in the hamster following chronic inhalation of RCF- 1, whereas the presence of short, thin fibers may play a role in the acute-phase biological response seen in both species.      

Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by human cytochrome P4501B1

Cytochrome P4501B1 (CYP1B1) is the most recently identified member of the dioxin-inducible CYP1 family. CYP1B1 is constitutively expressed in most human tissues, including colon and breast, and can activate numerous chemically diverse carcinogens. We evaluated the metabolism of the dietary heterocyclic amine carcinogen 2-amino-1-methyl-6- phenylimidazo[4,5-b]pyridine (PhIP) by microsomes from yeast expressing the human CYP1B1 protein. PhIP metabolites were analysed by HPLC with fluorescence and absorbance detection. We found that human CYP1B1 metabolizes PhIP to three products: N2-OH-PhIP, a mutagenic activation product; 4'-OH-PhIP, a detoxification product; and 2-OH-PhIP, the mutagenic potential of which is unknown. Metabolite identity was confirmed by co-elution with authentic standards and synchronous fluorescence spectroscopy. The identity of the 2-OH-PhIP standard was additionally confirmed by mass spectrometry. Kinetic studies of the formation of N2-OH-PhIP, 4'-OH-PhIP and 2-OH-PhIP by CYP1B1 indicated apparent Km values of 5.7 +/- 1.3, 2.2 +/- 0.5 and 1.3 +/- 0.2 microM, respectively. Apparent turnover rates were 0.40 +/- 0.03, 0.93 +/- 0.02 and 0.04 +/- 0.00 nmol product/min nmol P450, respectively. At saturating levels of substrate, CYP1B1-mediated formation of the non- mutagenic metabolite 4'-OH-PhIP was favored two-fold over that of the mutagenic metabolite, N2-OH-PhIP and >10-fold over that of 2-OH-PhIP. The formation of N2-OH-PhIP, a potent mutagen implicated in the etiology of human colon and breast cancer, indicates that CYP1B1 may play an important role in PhIP-mediated carcinogenesis.