Combination protocols of cytokine therapy with interleukin-3 and granulocyte-macrophage colony-stimulating factor in a primate model of radiation-induced marrow aplasia

Single cytokine therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) has been shown to be effective in decreasing the respective periods of neutropenia and thrombocytopenia following radiation- or drug-induced marrow aplasia. The combined administration of IL-3 and GM-CSF in normal primates suggested that a sequential protocol of IL-3 followed by GM-CSF would be more effective than that of GM-CSF alone in producing neutrophils (PMN). We investigated the therapeutic efficacy of two combination protocols, the sequential and coadministration of recombinant human IL- 3 and GM-CSF relative to respective single cytokine therapy, and delayed GM-CSF administration in sublethally irradiated rhesus monkeys. Monkeys irradiated with 450 cGy (mixed fission neutron:gamma radiation) received either IL-3, GM-CSF, human serum albumin (HSA), or IL-3 coadministered with GM-CSF for days 1 through 21 consecutively postexposure, or IL-3 or HSA for days 1 through 7 followed by GM-CSF for days 7 through 21. All cytokines and HSA were injected subcutaneously at a total dose of 25 micrograms/kg/d, divided twice daily. Complete blood counts (CBC) and platelet (PLT) counts were monitored over 60 days postirradiation. The respiratory burst activity of the PMN was assessed flow cytometrically, by measuring hydrogen peroxide (H2O2) production. Coadministration of IL-3 and GM-CSF reduced the average 16-day period of neutropenia and antibiotic support in the control animals to 6 days (P = .006). Similarly, the average 10-day period of severe thrombocytopenia, which necessitated PLT transfusion in the control animals, was reduced to 3 days when IL-3 and GM-CSF were coadministered (P = .004). The sequential administration of IL-3 followed by GM-CSF had no greater effect on PMN production than GM-CSF alone and was less effective than IL-3 alone in reducing thrombocytopenia. PMN function was enhanced in all cytokine-treated animals.     

Acute renal failure in a neonate due to pelviureteric candidal bezoars successfully treated with long-term systemic fluconazole

Systemic candidiasis with renal involvement is a rare but well-recognized complication during intensive care treatment in very-low-birth-weight infants. We report a term neonate who developed anuria associated with bilateral bezoar formation in the renal pelvis and candidemia. The treatment consisted of placement of a nephrostomy tube in the left kidney, short-term irrigation with amphotericin B and iv, and later, oral administration of fluconazole.     

Renal transplantation and osteoporosis

A cross sectional study assessed the bone mineral density (BMD) of 20 young adult patients who received a renal transplantation in childhood. The BMD of the lumbar spine, mainly trabecular bone, and of the total body, mainly cortical bone, were measured and expressed as an SD score. Fourteen patients (70%) had a BMD SD score of the lumbar spine below -1, of whom six patients were below -2. Fifteen patients (75%) had a BMD SD score of the total body below -1, of whom seven patients were below -2, Both trabecular and cortical bone appeared to be involved in the osteopenic process. The cumulative dose of prednisone was inversely correlated to both lumbar spine and total body BMD SD score. In a multiple regression analysis the cumulative dose of prednisone appeared to be the only factor with a significant effect on BMD SD score. Most young adult patients who had received a renal transplantation in childhood had moderate to severe osteopenia. Corticosteroid treatment played a major part in the development of osteopenia in these patients.     

Laparoscopic cholecystectomy and common bile duct exploration are safe for older patients

Background: Laparoscopic common bile duct (CBD) exploration is a well-established treatment option in dedicated centers. However, few data are available on the results in elderly patients. Methods: The outcome after laparoscopic CBD exploration in elderly patients (age <70 years) was compared with that in a concurrent control group of younger patients (age, <70 years). Results: There were 77 elderly patients in group A and 207 younger patients in group B. American Society of Anesthesiology (ASA) III and IV patients and prior abdominal operations were more frequent in group A (p <0.001). Two patients from each group underwent conversion to open surgery. There was no significant difference frequency of use between the transcystic and choledochotomy approaches, although the latter tended to be more frequent in the group A because of larger stones, (group A 53.4%; group B, 37.6%). Minor and major morbidity (group A, 12%; group B, 13.6%), rate of recurrent stones (group A, 1.3%; group B, 1.9%), and mortality (group A, 1.3%; group B, 0%) were not significantly different between the two groups. The single death in group A involved a patient with acute toxic cholangitis who underwent emergency surgery after multiple failed attempts at endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy performed elsewhere. No CBD stenosis was observed at follow-up assessment. Conclusions: Elective laparoscopic CBD exploration is safe and effective. It may become the standard of care in both elderly and younger patients.     

The Acute Dialysis Quality Initiative--part III: solute control (treatment dose)

One of the most important advances in chronic dialysis therapy was the establishment of a method for determining delivered dose. There has been a meaningful relationship between higher delivered dialysis dose and improved outcome in the end-stage renal disease (ESRD) patient. The question of establishing a similar dialysis dose method in the patients with acute renal failure (ARF) is hampered with several specific issues to the ARF patient. The state of catabolism in ARF is not eubolic, but rather catabolic. Patient volume or urea space is highly variable among ARF patients and even within the same patient over very short periods of time. Finally, there are comorbidities that play a major role in both the ultimate patient outcome and the generation of many of the indicators used in dialysis dose generation. Thus, the mere transition from the ESRD dose methodology, where these issues are quite stable, to the ARF population is not an easy process. It is, however, of utmost importance that a dose methodology be established. Only after will we be able to address the dose/outcome relationship. The current article reviews what is known, what is theorized and what needs to be established in an effort to determine a dialysis dose methodology in ARF patients.