Efficacy of multiple intraarterial papaverine infusions for improvement in cerebral circulation time in patients with recurrent cerebral vasospasm

OBJECT: Cerebral vasospasm that is caused by aneurysmal subarachnoid hemorrhage and that is refractory to maximal medical management can be treated with selective intraarterial papaverine infusions. The effects of single papaverine treatments on cerebral circulation time are well known. The purpose of this study was to assess the efficacy of multiple, repeated papaverine infusions on the cerebral circulation time in patients with recurrent vasospasm. METHODS: A retrospective study was conducted in 17 patients who received multiple intraarterial papaverine infusions in 91 carotid artery (CA) territories for the treatment of cerebral vasospasm. Cerebral circulation times were measured from the first angiographic image, in which peak contrast was seen above the supraclinoid internal CA, to the peak filling of cortical veins. Glasgow Outcome Scale (GOS) scores assessed 12 months after discharge were reviewed. Cerebral circulation times in 16 CA territories were measured in a control group of 11 patients. Seventeen patients received a total of 91 papaverine treatments. Prolonged cerebral circulation times improved after 90 (99%) of 91 papaverine treatments. The prepapaverine mean cerebral circulation time was 6.54 seconds (range 3.35-27 seconds) and the immediate postpapaverine mean cerebral circulation time was 4.19 seconds (range 2.1-12.6 seconds), an overall mean decrease of 2.35 seconds (36%, p < 0.001). Recurrent vasospasm reflected by prolonged cerebral circulation times continued to improve with subsequent papaverine infusions. Repeated infusions were just as successful quantitatively as the primary treatment (mean change 2.06 seconds). The mean cerebral circulation time in the control group was 5.21 seconds (range 4-6.8 seconds). In five patients a dramatic reversal of low-attenuation changes was detected on computerized tomography scans. The mean GOS score at 12 months after discharge was 3.4. CONCLUSIONS: The preliminary results indicate that multiple intraarterial papaverine treatments consistently improve cerebral circulation times, even with repeated infusions in cases of recurrent vasospasm.     

Association of renal adenocarcinoma and BK virus nephropathy post transplantation

While most BK virus infections are asymptomatic, immunosuppression has been associated with BK virus reactivation and impaired graft function or ureteric ulceration in renal transplant patients and hemorrhagic cystitis in bone marrow transplant patients. Oncogenicity is also postulated and this is the first report of a child with a carcinoma of the donor renal pelvis following BK virus allograft nephropathy. Removal of the primary tumor and cessation of immunosuppression led to regression of secondary tumors and a return to health.     

Anemia in pediatric renal transplant recipients

The aim of this study was to establish the prevalence of anemia in stable pediatric renal transplant recipients and to examine the association of anemia with renal function, immunosuppressants, angiotensin converting enzyme inhibitors, and growth, as well as iron, vitamin B₁₂, and folate stores. This is a cross-sectional study of the 50 renal transplant recipients currently followed at our center. Patient data were collected regarding hematological parameters, growth, medications, renal function, underlying renal disease, delayed graft function, episodes of rejection, and iron or erythropoietin therapy post transplantation. The mean hemoglobin level (Hb) was 110 g/l and the overall prevalence of anemia was 60%, including 30% who were severely anemic (Hb<100 g/l). There was a high rate of iron deficiency (34%) and serum iron was the parameter of iron metabolism most closely associated with anemia. Hb in patients with low serum iron was 90.7 g/l versus 114.4 g/l in those with normal serum iron (P<0.01). Both univariate and multiple linear regression determined tacrolimus dose and creatinine clearance to be significant factors associated with anemia. Tacrolimus dose correlated with a 10 g/l reduction in Hb for every increase of tacrolimus dose of 0.054 mg/kg per day (P=0.001). The dose of mycophenolate was positively correlated with Hb, but this was likely to be confounded by our practice of dose reduction in the setting of anemia. Angiotensin converting enzyme inhibitor use was not associated with anemia. Severely anemic patients tended to be shorter, with a mean Z-score for height of –1.8 compared with –0.9 for those with normal Hb (P=0.02). Anemia is a significant and common problem in pediatric renal transplant patients. Deteriorating renal function is an important cause, but other factors like iron deficiency and immunosuppression are involved. Definition of iron deficiency is difficult and serum iron may be a valuable indicator. Medication doses, nutritional status, need for erythropoietin and iron, as well as poor graft function and growth require systematic scrutiny in the care of the anemic renal transplant recipient.     

Diagnosis of patent foramen ovale with multiplane transesophageal echocardiography in adult cardiac surgical patients

OBJECTIVE: To evaluate multiplane transesophageal echocardiography (TEE) for detection of patent foramen ovale (PFO) and to compare multiplane TEE with visual inspection (VI) for PFO detection. DESIGN: A prospective observational study. SETTING: University hospital (single institution). PARTICIPANTS: Patients presenting for cardiac surgery requiring TEE. INTERVENTIONS: Multiplane TEE including 2 atrial views with color-flow Doppler (CFD) and contrast echocardiography (CE) with a provocative respiratory maneuver (PRM) and comparison of multiplane TEE and VI with respect to PFO detection. MEASUREMENTS AND MAIN RESULTS: The cohort size was 187. PFO prevalence was 27.3%. CFD with serial decrease of the Nyquist limit detected 51% of all PFO: 41.2% in the bicaval view alone, 27.5% in the 4-chamber view alone, and 9.8% in both views. CE detected 78.4% of all PFO: 72.5% with PRM, 45.1% with no PRM, and 27.4% with/without PRM. PFO detection by multiplane TEE and visual inspection were correlated in 41 subjects. TEE diagnosed 11 PFO (26.8% prevalence, 3 missed by VI). VI diagnosed 12 PFO (29.3% prevalence, 4 missed by TEE). CONCLUSIONS: Multiplane TEE is a gold standard for detection of PFO. Despite advances in TEE technology, 2-dimensional imaging does not detect all PFO. To maximize PFO detection, multiple TEE modalities are required in multiple views, despite a low Nyquist limit for CFD or a PRM for CE. Even though multiplane TEE is equivalent to VI for PFO detection, the discrepancy rate may be an important consideration in the individual case.     

Loss of captopril-bound Fe by end-stage renal failure patients during hemodialysis

BACKGROUND: Patients on chronic hemodialysis often suffer from severe anemia, the outcome of iron deficiency and inadequate response to erythropoietin. Antihypertensive treatment with captopril worsens anemia, erythropoietin production and iron balance in hemodialysis patients. We investigated the possibility that iron chelation by captopril in the blood may result in elimination of iron-captopril complexes during hemodialysis, thus minimizing the effect of both medications. METHODS: Twelve hypertensive hemodialysis patients (group 1) were treated with 12.5 mg/day captopril, while their 12 counterparts received 1.25 mg/day ramipril. Following two weeks of treatment and two weeks of "washout", captopril in group 1 was substituted with ramipril and ramipril in group 2 was replaced by captopril for an additional two week period. Blood and dialysate samples were procured at the beginning and the end of the dialysis, for iron, aluminum, transferin, ferritin, hemoglobin (Hb) and hematocrit (Htc) determination. RESULTS: Iron, ferritin, transferin, Hb and Htc were decreased in the captopril-treated group 1. They similarly decreased in group 2 following replacement of ramipril by captopril for an additional period of two weeks. Significant amounts of iron were detected in dialysates of captopril, but not ramipril-treated patients. At the end of the dialysis, iron content was further increased in dialysates of the captopril-treated groups. CONCLUSIONS: 1) Captopril-chelated iron is eliminated in dialysis fluid during the dialysis session, apparently contributing to captopril-related anemia in patients on chronic hemodialysis. 2) Antihypertensive treatment with angiotensin converting enzyme (ACE) inhibitors other than captopril might prove advantageous for this patient category.     

Coelacanth genome sequence reveals the evolutionary history of vertebrate genes

The coelacanth is one of the nearest living relatives of tetrapods. However, a teleost species such as zebrafish or Fugu is typically used as the outgroup in current tetrapod comparative sequence analyses. Such studies are complicated by the fact that teleost genomes have undergone a whole-genome duplication event, as well as individual gene-duplication events. Here, we demonstrate the value of coelacanth genome sequence by complete sequencing and analysis of the protocadherin gene cluster of the Indonesian coelacanth, Latimeria menadoensis. We found that coelacanth has 49 protocadherin cluster genes organized in the same three ordered subclusters, alpha, beta, and gamma, as the 54 protocadherin cluster genes in human. In contrast, whole-genome and tandem duplications have generated two zebrafish protocadherin clusters comprised of at least 97 genes. Additionally, zebrafish protocadherins are far more prone to homogenizing gene conversion events than coelacanth protocadherins, suggesting that recombination- and duplication-driven plasticity may be a feature of teleost genomes. Our results indicate that coelacanth provides the ideal outgroup sequence against which tetrapod genomes can be measured. We therefore present L. menadoensis as a candidate for whole-genome sequencing.