Nitric oxide/platelet activating factor cross-talk in mesangial cells modulates the interaction with leukocytes

BACKGROUND: The secondary hyperparathyroidism of chronic kidney disease (CKD) produces a high turnover osteodystrophy that is associated with peritrabecular fibrosis. The nature of the cells involved in the development of peritrabecular fibrosis may represent osteoprogenitors expressing a fibroblastic phenotype that are retarded from progressing through osteoblast differentiation. METHODS: To test the hypothesis that osteoblast differentiation is retarded in secondary hyperparathyroidism due to CKD producing bone marrow fibrosis, we administered bone morphogenetic protein 7 (BMP-7), a physiologic regulator of osteoblast regulation, to C57BL6 mice that had CKD produced by electrocautery of one kidney followed by contralateral nephrectomy two weeks later. Following the second surgical procedure, a subgroup of mice received daily intraperitoneal injections of BMP-7 (10 microg/kg). Three to six weeks later, the animals were sacrificed, blood was obtained for measurements of blood urea nitrogen (BUN) and parathyroid hormone (PTH) levels, and the femora and tibiae were processed for histomorphometric analysis. RESULTS: The animals had significant renal insufficiency with BUN values of 77.79 +/- 22.68 mg/dL, and the level of renal impairment between the CKD untreated mice and the CKD mice treated with BMP-7 was the same in the two groups. PTH levels averaged 81.13 +/- 51.36 and 75.4 +/- 43.61 pg/mL in the CKD and BMP-7 treated groups, respectively. The animals with CKD developed significant peritrabecular fibrosis. In addition, there was an increase in osteoblast surface and osteoid accumulation as well as increased activation frequency and increased osteoclast surface consistent with high turnover renal osteodystrophy. Treatment with BMP-7 eliminated peritrabecular fibrosis, increased osteoblast number, osteoblast surface, mineralizing surface and single labeled surface. There was also a significant decrease in the eroded surface induced by treatment with BMP-7. CONCLUSIONS: These findings indicate that BMP-7 treatment in the setting of high turnover renal osteodystrophy prevents the development of peritrabecular fibrosis, affects the osteoblast phenotype and mineralizing surfaces, and decreases bone resorption. This is compatible with a role of osteoblast differentiation in the pathophysiology of osteitis fibrosa.     

Sympathetic skin response evoked by laser skin stimulation

The objective of this study was to evoke sympathetic skin responses (SSRs) in healthy subjects using laser stimulation and to compare these responses with those induced by conventional electrical stimuli. Twenty healthy subjects were investigated. SSRs were obtained using electrical and laser stimuli delivered to the wrist controlateral to the recording site. The sympathetic sudomotor conduction velocity (SSFCV) was measured in 8 subjects by simultaneously recording the SSR from the hand and the axilla. The latency (L) of the laser-induced SSR (ISSR) was significantly longer than that of the electrically-evoked SSR (eSSR) (mean ISSRL= 1.7 +/- 0.145 ms, mean eSSRL= 1.56 +/- 0.14 ms, p<0.05). The amplitude (A) of the ISSR was lower than the eSSR amplitude (mean ISSRA = 1.31 +/- 0.26 mV, mean eSSRA = 2.59 +/- 0.49 mV, p<0.05). No significant difference between the ISSR and eSSR was observed in either the SSFCV or the variability and reproducibility parameters. Our findings show that SSRs can easily be induced by laser stimuli and that this method shares the technical limitations of conventional eSSRs.     

Pre-perceptual pain sensory responses (N1 component) in type 1 diabetes mellitus

We investigated the integrity of the ascending pathways for pain sensitivity in the early stage of type 1 diabetes mellitus, by measuring the N1 component and the conventional N2/P2 vertex potentials of laser evoked potentials (LEPs). Brain responses to laser stimuli were obtained in 21 healthy volunteers and 21 type 1 diabetic patients, without either clinical neuropathy or electrophysiological evidence of large-fiber damage. In diabetic patients N1 and P2 latencies were prolonged and the N1 and N2/P2 amplitudes were decreased after foot stimulation. A significant reduction of the conduction velocity of Adelta fibers in the lower limbs was also observed. LEPs reveal an early, subclinical and selective damage of pain sensation in diabetic patients. N1 and P2 potentials are delayed and decreased in parallel giving evidence that LEP abnormalities are not secondary to a cognitive dysfunction and mostly reflect a small-fiber dysfunction.     

High-dose cytarabine as consolidation treatment for patients with acute myeloid leukemia with t(8;21)

Seventeen patients affected by acute myeloid leukemia (AML) with t(8;21) were prospectively programmed to receive three courses of high-dose cytarabine (HDARA-C) as post-remission therapy. The median age was 39 years and in all cases t(8;21) was the only karyotypic abnormality. Complete remission (CR) was achieved in 14 out of 17 cases (82%) and, after first consolidation with NOVIA regimen (intermediate dose ARA-C plus mitoxantrone), all patients received the three planned courses of HDARA-C (3g/m(2) q12h on days 1, 3, 5). There were two documented infections, while all patients experienced fever of unknown origin (FUO). Nonhematological toxicity was mild. Thirteen out of 14 patients are in continuous CR after a median follow-up of 44 months. One patient relapsed at 16 months and, following CR2 achievement, underwent allogeneic transplantation; he died 3 months later while in CR from acute graft versus host disease (GVHD). Survival at 5 years is projected at 79%. Our data confirm the efficacy of repeated courses of HDARAC for patients with t(8;21) AML.     

Clinical utilization of the coronary pressure wire

INTRODUCTION: Earlier studies have established the value of coronary pressure wires for diagnosing and monitoring the treatment of patients with coronary artery disease. In this study we demonstrated their usefulness in the daily clinical practice of a catheterization laboratory. MATERIAL AND METHODS: A retrospective study of the use of pressure wires in our laboratory between October 1998 and November 2000. The pressure wire was inserted whenever the interventional cardiologist considered it to be indicated. In all cases, pressures were recorded with a Waveguide Cardiometrics 0.014 guide (Endosonics) and hyperemia was induced by intracoronary adenosine. RESULTS: Two hundred fifty-three lesions were studied in 190 patients. Indications were functional evaluation of lesions of intermediate severity for 82% (9% intrastent restenoses); guidance of balloon PTCA for 5%; and fulfillment of a research protocol for 13%. Twenty-six percent of lesions considered to be of moderate severity based on angiography were treated as a consequence of the pressures measured by the wire. A decision to begin or continue a procedure was based on wire pressures in 24% and intervention was avoided in 60%. No major complications attributable to the wire were observed. A lesion was dissected in one patient (0.5%) but it was treated without consequences. Twenty pressure wires (11%) failed to work properly during the procedure, fourteen of them (7%) before insertion. The wire could not be advanced across the lesion in one case. CONCLUSIONS: The pressure wire is useful in the daily clinical practice of a catheterization laboratory. Its most common indication is the evaluation of lesions of intermediate or unknown severity, and use is associated with few complications.     

Portomesenteric vein gas: diagnostic and prognostic value

Portomesenteric pneumatosis has been traditionally associated with intestinal infarction and poor outcome; however, recent studies have questioned its clinical value. To assess its diagnostic and prognostic significance we have retrospectively evaluated 47 patients correlating the CT finding of portomesenteric vein gas with clinical data and outcome. Thirty-nine patients (83%) had surgical evidence of intestinal infarction, four had necrotic small bowel volvulus (8.5%), two had blunt trauma, one had necrotic gastric volvulus, and one a gastric mucosal lesion induced by a nasogastric tube. Fifteen patients survived (31.9%); only 8/39 patients with intestinal infarction survived. Portomesenteric pneumatosis is a reliable marker of intestinal infarction and poor outcome; however, in trauma patients this sign is associated with a better prognosis. Electronic Publication