The biological and economic value of oral organic iron in maintenance dialysis

With the widespread use of recombinant erythropoietin (EPO) for patients with end-stage renal disease (ESRD), management of iron deficiency is an ongoing issue for the renal team. Effective iron replacement and maintenance play a vital role in efficient use of EPO. For hemodialysis patients, intravenous (i.v.) iron has proven convenient and, as an ancillary drug outside of the composite rate, generates profits for dialysis facilities. Improvements in the vehicle with which i.v. iron is administered have led to a reduction in severe or fatal reactions common with iron dextran products. Oral iron has had a spotty track record as an effective therapy for dialysis patients. Compliance has been hindered by patient discomfort when taking oral iron. Patients on peritoneal dialysis and those with chronic kidney disease remain good candidates for oral iron because of convenience, and oral formulas could prove more effective even in the hemodialysis patient population if they were better tolerated and better absorbed, and if using them would not place an economic burden on the patient and/or an economic hardship on the facility. In a capitated/bundled payment environment, oral iron may become a blessing rather than a curse for facilities that need to find more economic ways of providing services. Heme-iron, now undergoing clinical studies, may be a reliable replacement for i.v. iron in that scenario.     

Comparison of two drug regimens upon clinical outcome among renal transplant recipients with positive flow cytometric crossmatches

Renal transplant recipients with positive flow cytometric crossmatches (FCXM) face greater risk of early rejection and graft failure. It is clear that the pharmacologic needs of this high risk group have not been identified. We retrospectively compared the impact of two drug regimens upon early rejection and 5 yr actuarial survival among 324 primary cadaveric transplant recipients with positive and negative FCXM. Patients received either Regimen I (OKT3 induction, cyclosporine and steroids) or Regimen II (mycophenolate mofetil with cyclosporine or Prograf). Recipient gender, age, disease etiology, ethnic distribution and cytotoxic panel reactive antibody (PRA) were equivalent between regimens (p=ns). With Regimen I, the incidence of rejection was greater for FCXM positive vs. FCXM negative patients (51 vs. 21%, p=0.001). In contrast, with Regimen II the incidence of rejection for FCXM positive and FCXM negative patients was equivalent (18 vs. 12%, p=ns) and lower than patients treated with Regimen I (p < 0.01). Ethnic variation was only observed with Regimen I in which African Americans with positive FCXM had more rejections than Caucasians (60 vs. 45%, p < 0.05). Five-year actuarial survival was lower for FCXM positive vs. FCXM negative patients treated with Regimen I (40 vs. 75%, p=0.0006) or Regimen 2 (60 vs. 90%, p=0.001). Allograft survival was equivalent (p=ns) among FCXM positive individuals receiving Regimen I or II. However, allograft survival among FCXM negative individuals improved with Regimen II (p < 0.05). Ethnic variation in survival was not observed with either regimen (p=ns).     

Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa

PURPOSE: The objective of the present study was to evaluate the therapeutic efficacy of ciliary neurotrophic factor (CNTF) delivered through encapsulated cells directly into the vitreous of the eye in an rcd1 canine model of retinitis pigmentosa. The dose-range effect of the treatment was also investigated. METHODS: Polymer membrane capsules (1.0 cm in length and 1.0 mm in diameter) were loaded with mammalian cells that were genetically engineered to secrete CNTF. The cell-containing capsules were then surgically implanted into the vitreous of one eye of rcd1 dogs at 7 weeks of age, when retinal degeneration is in progress but not complete. The contralateral eyes were not treated. The capsules remained in the eyes for 7 weeks. At the end of the studies, the capsules were explanted, and CNTF output and cell viability were evaluated. The eyes were processed for histologic evaluation. RESULTS: In each animal, the number of rows of photoreceptor nuclei in the outer nuclear layer (ONL) was significantly higher in the eye that received a CNTF-secreting implant than in the untreated contralateral eye. No adverse effects were observed on the retina in the treated eyes. The explanted capsules produced a low level of CNTF. The cells in the capsules remained viable and densely distributed throughout. CONCLUSIONS: CNTF delivered through encapsulated cells directly into the vitreous of the eye protects photoreceptors in the PDE6B-deficient rcd1 canine model. Furthermore, sparing of photoreceptors appeared dose-dependent with minimum protection observed at CNTF doses of 0.2 to 1.0 ng/d. Incrementally greater protection was achieved at higher doses. The surgically implanted, cell-containing capsules were well tolerated, and the cells within the capsule remained viable for the 7-week implantation interval. These results suggest that encapsulated cell therapy may provide a safe and effective strategy for treating retinal disorders in humans.     

Qualitative findings on the experience of end-of-life care for hematological malignancies

There is a loud silence in the literature on the issues related to palliative care for hematological malignancies. This article presents information that begins to address that silence. The limited research that is available indicates that, to date, patients with a hematological malignancy and their families received scant attention with regards to the provision of palliative care. The findings presented in this article demonstrates that families are enduring considerable hardship and are left with much emotional pain and many unresolved issues when such care is not offered. It is hoped that the findings presented in this article will be used for developing effective strategies to ensure that patients with hematological malignancies and their families, no less than any others, can be afforded the dignity and respect that the appropriate provision of palliative services ensures.     

Synthesis of ketone analogues of prolyl and pipecolyl ester FKBP12 ligands

The recently discovered small-molecule ligands for the peptidyl and prolyl isomerases (PPIase) of FKBP12 have been shown to possess powerful neuroprotective and neuroregenerative effects. Ketone analogues of the prolyl and pipecolyl esters, which mimic only the FKBP binding domain portion of FK506, are proposed and an efficient synthetic strategy is presented in this report, along with the preliminary results of in vitro and in vivo biological studies.     

Amodiaquine treatment of uncomplicated malaria in children, in an area of chloroquine-resistant Plasmodium falciparum in north-central Nigeria

The efficacy of amodiaquine against Plasmodium falciparum malaria was assessed in an area of confirmed chloroquine resistance in the cool, north-central plateau of Nigeria, using a 14-day protocol. The patients were all children aged <5 years of age. The drug proved highly efficacious, giving a cure 'rate' of 100% on day 14 and mean fever- and parasite-clearance times of 1.11 and 3.11 days, respectively. It was also well tolerated. Following treatment, packed-cell volumes (PCV) generally increased (65% of patients) but remained constant (12%) or even decreased (23%) in some patients; the overall improvement in PCV was not statistically significant (P >0.05). The results justify the use of amodiaquine to treat P. falciparum malaria in those who have failed treatment with chloroquine and the second-line drugs (e.g. sulfadoxine-pyrimethamine) currently used in Nigeria. As the amodiaquine would be better employed as one part of a combination than on its own, there is a need to identify suitable partner compounds.     

Practical aspects of performance improvement in pediatric trauma

Pediatric trauma performance improvement programs may share some of the criteria tracked by their counterparts in the adult trauma world. However, some of the criteria must be specific to the unique diagnostic and therapeutic needs of children. Nine criteria are defined in terms of the critical issues, what information is required to evaluate the appropriateness of the care provided in regards to those issues, and acceptable thresholds for review. In addition, practical aspects of multi-disciplinary peer review in the performance improvement process is presented.