Diffusion-weighted MR imaging of kidneys in healthy volunteers and patients with parenchymal diseases: initial experience

PURPOSE: To prospectively evaluate feasibility of diffusion-weighted (DW) magnetic resonance (MR) imaging in assessment of renal function in healthy volunteers and patients with various renal abnormalities and to prospectively evaluate reproducibility of DW MR imaging in volunteers. MATERIALS AND METHODS: Study protocol was approved by local ethics committee; informed consent was obtained. Eighteen healthy volunteers and 15 patients underwent transverse fat-saturated echo-planar DW MR imaging of the kidneys during normal breathing. Freehand regions of interest were delineated in the cortex and medulla of the kidneys. The following apparent diffusion coefficient (ADC) values were calculated: ADC of all b values (ADC(avg)), ADC of low b values (b = 0, 50, 100 sec/mm2; ADC(low)), and ADC of high b values (b = 500, 750, 1000 sec/mm2; ADC(high)). These values were calculated to differentiate influence of perfusion and diffusion. Reproducibility was assessed by repeating the same protocol in five randomly selected volunteers after 6 months. For statistical analysis, Student t tests were used. RESULTS: In all volunteers, ADC(avg) and ADC(high) were significantly higher in the cortex than in the medulla (P < .001). No difference between the cortex and medulla could be observed for ADC(low). Patients with renal failure had significantly lower ADC(avg) (P < .001, P = .004), ADC(low) (P = .02, P = .03), and ADC(high) (P = .02, P = .04) of cortex and medulla, respectively, than did volunteers. In the patient with pyelonephritis, all ADC values of cortex and medulla were substantially lower compared with the contralateral side, whereas patients with ureteral obstruction showed varying degrees of difference in all ADC values compared with the contralateral side. No statistically significant changes were found in the repeat study of the volunteers. CONCLUSION: DW MR imaging is feasible and reproducible in the assessment of renal function, as shown in our initial experience with a small number of patients and volunteers.     

Neutrophil migration and production of reactive oxygen species during treatment with a fully human anti-tumor necrosis factor-alpha monoclonal antibody in patients with rheumatoid arthritis

OBJECTIVE: To evaluate the effects of therapy with a fully human anti-tumor necrosis factor (TNF)-alpha monoclonal antibody on the production of superoxide and other reactive oxygen species (ROS) and on the migration capacity of neutrophils in patients with rheumatoid arthritis (RA). METHODS: A total of 29 patients with active RA and 25 healthy controls participated. Assessments were performed at baseline and 2 weeks after the first administration of anti-TNF-alpha. The production of ROS was studied in unstimulated conditions and after stimulation of receptor dependent (serum treated zymosan, STZ) and receptor independent (phorbol mystrate acetate, PMA) pathways by luminol enhanced chemiluminescence. As well, the PMA induced burst production of superoxide was measured using the cytochrome-c reduction assay. Potential changes in neutrophil migration to joints were assessed by scintigraphy with autologous leukocytes. RESULTS: Baseline production of ROS (both spontaneously and after STZ stimulation) and superoxide and the ex vivo chemotaxis were similar in RA patients (n = 25) and controls (n = 25) and remained unchanged after administration of anti-TNF-alpha. The production of ROS after PMA stimulation was slightly higher in patients than in controls (p = 0.04) and this difference disappeared 2 weeks after the first dose of anti-TNF-alpha (p < 0.05). The scintigraphic study showed that a single dose of anti-TNF-alpha, but not placebo, markedly decreased the influx of leukocytes to inflamed joints. CONCLUSION: In patients with RA, anti-TNF-alpha therapy rapidly decreases the influx of leukocytes into inflamed joints but does not impair neutrophil chemotaxis and production of ROS.     

The first 2 years of a palliative care consultation team in the Netherlands

In January 1999 an integrated multidisciplinary palliative care consultation (PCC) team was established in Maastricht in the Netherlands. The team included experts in palliative care who had extensive experience in a variety of settings. One of the major tasks of the PCC team was to give support, information and advice to healthcare professionals caring for terminally ill patients. The PCC team was asked by the government to consecutively register and evaluate all consultations. This article describes these consultations, including information on the requesting caregivers, the patients, the questions asked and the recommendations given in the first 26 months. The results show that the PCC team served the needs of professional caregivers in a variety of settings. Most consultations concerned physical and pharmacological problems and the majority of recommendations were evaluated as positive.     

MicroCRP: a highly sensitive CRP method applied in the monitoring of renal allograft recipients

A new ultrasensitive fluoroimmunometric assay for C-reactive protein (CRP), called MicroCRP assay, has a lower detection limit of 0.05 mg/l, and a CV of 7.6% at concentration 0.25 mg/l. The microCRP levels in healthy adults show a skewed distribution, median 0.90 mg/l and mean 1.4 mg/l, with 2.5th and 97.5th percentiles of 0.17 and 4.7 mg/l, respectively, and no gender-related or age differences. Serial microCRP was applied in the monitoring of 37 renal allograft recipients. The operative trauma gave rise to an initial CRP peak, usually on day 2 after transplantation, with a return to preoperative value 1 week after surgery. There were significant CRP elevations (>25%) in all cases of rejections, indicating 100% sensitivity. The microCRP values started to increase about 3 days (range -1 to 9 days) before the rise in creatinine. The microCRP peak tended to be higher in rejection episodes with a vascular component, compared with episodes of cellular rejection (p=0.05). A rise in microCRP at days 7-12 after transplantation seems to predict the risk of rejections later on, and probably reflects the primary immune response to the graft. Recipients without this primary CRP response (only 6 of 37 patients) subsequently had uncomplicated courses. Tracking of values below the traditional lower limit is essential in order to recognize the different CRP peaks. Serial monitoring of microCRP is well suited for clinical use and provides clinical information previously unattainable with other assay systems.     

Chronic Arsenic Poisoning From Burning High-Arsenic-Containing Coal In Guizhou, China

Optimization of a previously disclosed sorbitol dehydrogenase inhibitor (SDI, II) for potency and duration of action was achieved by replacing the metabolically labile N,N-dimethylsulfamoyl group with a variety of heterocycles. Specifically, this effort led to a series of novel, in vitro potent SDIs with longer serum half-lives and acceptable in vivo activity in acutely diabetic rats (e.g., 62, 67, and 69). However, the desired in vivo potency in chronically diabetic rats, ED90 less than or equal to 5 mg/kg/day, was achieved only through further modification of the piperazine linker. Several members of this family, including 86, showed better than the targeted potency with ED90 values of 1-2 mg/kg/day. Compound 86 was further profiled and found to be a selective inhibitor of sorbitol dehydrogenase, with excellent pharmacodynamic/pharmacokinetic properties, demonstrating normalization of sciatic nerve fructose in a chronically diabetic rat model for approximately 17 h, when administered orally at a single dose of 2 mg/kg/day.