The detection of monocytes in human glomerulonephritis

Renal biopsy specimens from 343 patients with primary or secondary glomerulonephritis (GN) were examined for monocytes by the non-specific esterase reaction. Large numbers of monocytes per glomerulus (M/G) were found in essential cryoglobulinemia GN (29 pts, M/G 30.6 +/- 22.4), in acute post-infectious GN (27 pts, M/G 9.1 +/- 8.3), in rapidly progressive crescentic GN (20 pts, M/G 5.6 +/- 2.7), in systemic lupus GN (61 pts, M/G 5.0 +/- 5.6), and in IgA-GN associated with chronic liver disease (5 pts, M/G 6.4 +/- 5.9) or Sch?nlein-Henoch purpura (15 pts, M/G 3.3 +/- 6.4). Clinico-histological correlation showed that monocyte infiltration was correlated with the extent of proteinuria (all groups), with the presence of endoluminal "thrombi" (cryoglobulinemia GN), of polymorphonuclear leukocyte infiltration (post-infectious GN), of cellular crescents (crescentic GN), of "active" lesions (lupus GN), and with the extension of lesions to the peripheral capillary walls (IgA-associated GN). The M/G index was negligible in renal amyloidosis (21 pts), in idiopathic membranoproliferative GN (10 pts), in idiopathic IgA mesangial GN (63 pts), in membranous GN (40 pts), in focal glomerulosclerosis (29 pts), in minimal change nephropathy (18 pts), and in diabetic glomerulosclerosis (5 pts). The results confirm the participation of cells of the monocyte-macrophage series in the genesis of proliferative lesions, both intracapillary and extracapillary, in immune-mediated human GN and suggest their direct involvement in glomerular injury.     

Timing of cranial reconstruction after cranioplasty infections: are we ready for a re-thinking? A comparative analysis of delayed versus immediate cranioplasty after debridement in a series of 48 patients

Neurosurgical Review - The optimal management of cranioplasty infections remains a matter of debate. Most authors have suggested that the infected bone/implant removal is mandatory, combined with...     

On-line urea kinetics in haemodiafiltration

BACKGROUND.: Calculation of Kt/V and assessment of nutrition have so farbeen dependent upon off-line urea measurements of blood or dialysatesamples. Here we describe a biosensor for on-line urea measurementduring haemodiafiltration. METHODS.: The biosensor consisted of a cartridge containing covalentlylinked urease placed between two conductivity cells. The biosensorwas placed on the outlet line of a haemofilter in series witha dialyser in order to obtain an aliquot of plasma ultrafiltratefor on-line measurement of urea. RESULTS.: Urea nitrogen concentrations were highly correlated to the difference() in conductivity measured by the two conductivity cells bothin aqueous solutions (in-vitro studies, y=–6.676+32.12x,R²=0.998, P<0.0001) and in ultrafiltrates (ex-vivo studies,y=–6.7+32.01x, R²=0.98, P<0.00001). conductivity washighly reproducible (% variation: 0.8–5.3%) and stable(maximal % variation at 150 mg/dl after 180 min: 0.9±0.3vs initial values). The intradialytic plasma water urea profilewas obtained in 10 haemodialysis patients. To study recirculation,the plasma water urea profile was analysed before and 3 minafter stopping the dialysate flow. The pre- and post-stoppedflow ratio (1.21±0.1, mean±1 SD) was superimposableto conventional blood sampling data (opposite arm venous/arterial:1.22±0.11) and allowed correction for recirculation.A novel approach to urea kinetic modelling was described andused to reliably project end-dialysis and post-dialysis reboundurea concentration as early as 90 min. Projected (29.2±10.4g) or measured (29.8±10.5 g) net urea removal was highlycorrelated with the amount of urea collected in the total spentdialysate (29.7±10.6 g) (R²=0.99, R²=0.97 respectively). CONCLUSIONS.: These results indicate that on-line, real-time analysis of ureakinetics may provide information on delivery of adequate dialysisin high-efficiency techniques.     

S-glutathionylation of metallothioneins by nitrosative/oxidative stress

Cystein residues within metallothionein (MT) structure have been shown to be particularly prone to S-nitrosylation. The objective of this study was to examine the possibility that MTs undergo S-glutathionylation under nitrosative/oxidative stress. MT from rabbit liver was treated with different concentrations of GSNO, diamide plus GSH or H₂O₂ plus GSH. Parallel sets of samples were treated with 10 mM DTT for 30 min at 37 °C to reduce mixed disulphides. Incubations were then processed for Western blot or dot-immunobinding assay. Western blot with anti-MT or anti-GSH were also performed on peripheral blood mononuclear cell extracts. Structural aspects of S-glutathionylation of MTs were also examined. Treatment with GSNO, diamide/GSH or H₂O₂/GSH induced a dose-dependent increase in the levels of MT S-glutathionylation. This effect was completely reversed by treatment with the reducing agent DTT, indicating that S-glutathionylation of MT protein was related to formation of protein-mixed disulphides. Structural analysis of rat MT indicated that Cys residues located in the N-terminal domain of the protein are the likely targets for S-glutathionylation, both for their solvent accessibility and electrostatics induced reactivity. S-Glutathionylation of MT, given its reversibility, would provide protection from irreversible oxidation of Cys residues, thus representing a mechanism of high potential biological relevance.     

In Vivo Imaging of Cerebral Dopamine D3 Receptors in Alcoholism

Animal studies support the role of the dopamine D3 receptor (DRD3) in alcohol reinforcement or liking. Sustained voluntary alcohol drinking in rats has been associated with an upregulation of striatal DRD3 gene expression and selective blockade of DRD3 reduces ethanol preference, consumption, and cue-induced reinstatement. In vivo measurement of DRD3 in the living human brain has not been possible until recently owing to a lack of suitable tools. In this study, DRD3 status was assessed for the first time in human alcohol addiction. Brain DRD3 availability was compared between 16 male abstinent alcohol-dependent patients and 13 healthy non-dependent age-matched males using the DRD3-preferring agonist positron emission tomography (PET) radioligand [¹¹C]PHNO with and without blockade with a selective DRD3 antagonist (GSK598809 60 mg p.o.). In striatal regions of interest, where the [¹¹C]PHNO PET signal represents primarily DRD2 binding, no differences were seen in [¹¹C]PHNO binding between the groups at baseline. However, baseline [¹¹C]PHNO binding was higher in alcohol-dependent patients in hypothalamus (V_T: 16.5±4 vs 13.7±2.9, p=0.040), a region in which the [¹¹C]PHNO signal almost entirely reflects DRD3 availability. The reductions in regional receptor binding (V_T) following a single oral dose of GSK598809 (60 mg) were consistent with those observed in previous studies across all regions. There were no differences in regional changes in V_T following DRD3 blockade between the two groups, indicating that the regional fractions of DRD3 are similar in the two groups, and the increased [¹¹C]PHNO binding in the hypothalamus in alcohol-dependent patients is explained by elevated DRD3 in this group. Although we found no difference between alcohol-dependent patients and controls in striatal DRD3 levels, increased DRD3 binding in the hypothalamus of alcohol-dependent patients was observed. This may be relevant to the development of future therapeutic strategies to treat alcohol abuse.     

Characterization of interstitial infiltrating cells in Berger's disease

The role of infiltrating blood-borne cells in the pathogenesis of renal damage in human glomerulonephritis is under active investigation. We have evaluated leukocyte infiltrates (number of cells/mm2) in the renal interstitium of 21 patients with Berger's disease and eight normal kidneys with monoclonal antibodies and a four-layer immunoperoxidase technique. In our population of patients, the number of infiltrating T-lymphocytes (OKT11+ cells) was significantly higher (median, 132) than in the normal kidneys (median, 60). This increase was mainly due to T-suppressor/cytotoxic lymphocytes (OKT8+ cells; median, 68), while T-helper/inducer lymphocytes (Leu 3A+ cells) and monocytes were in the normal range. T-lymphocyte infiltration was more marked in ten patients with impaired glomerular filtration rate (GFR) at the time of biopsy (median, 167) than in patients with normal GFR (median, 88). In addition, ten patients who showed deterioration of renal function during the subsequent follow-up, whatever their serum creatinine levels at the time of biopsy, had significantly more total T cells (median, 269), OKT8+ cells (median, 143), and Leu 3A+ cells (median, 105) than 11 patients with persistently stable GFR and normal controls. More data are necessary to establish whether this T-lymphocyte infiltration is the consequence of a cell-mediated mechanism acting in the interstitium, concomitant with the immune-complex-mediated mechanism acting in the glomerulus, or is a nonspecific consequence of the tubulointerstitial damage induced by the immunologically mediated glomerular disease.     

The ALPPS Procedure: A Surgical Option for Hepatocellular Carcinoma with Major Vascular Invasion

Background

Hepatocellular carcinoma (HCC) tends to have a particular invasiveness toward the portal vein (PV) branches and hepatic veins. This situation can hamper major surgical resection with a risk of postoperative liver failure due to the small future liver remnant (FLR) in cirrhotic livers. These patients are then usually directed to palliative treatments with poor results. The associating liver partition and PV ligation (PVL) in staged hepatectomy (ALPPS) strategy is one of the main surgical innovations in recent years in the field of liver surgical oncology. The ALPPS approach could allow surgical resection in patients with HCC and associated major vascular invasion.

Methods

Among 1,143 liver resection performed in our center, the ALPPS approach was employed in order to induce rapid hypertrophy of the left FLR in patients with HCC and associated major vascular invasion. This strategy consists of combining the in situ splitting of the liver along the main portal scissura or on the right side of the falciform ligament and PVL in a strategy of staged hepatectomy.

Results

In our experience the ALPPS approach allowed us to achieve a sufficient FLR in two cases of HCC with major vascular invasion, in which the classic two-stage strategy could not be applied. In both cases the patients could undergo major hepatectomies without mortality.

Conclusions

This novel strategy could expand the number of patients undergoing major liver resections that were previously considered non-resectable because of the risk of liver decompensation for an insufficient FLR.     

Responsiveness of the rabbit eye to adrenergic and cholinergic agonists after treatment with 6-hydroxydopamine or alpha-methyl-para-tyrosine: part II--intraocular pressure changes.

The influence of adrenergic and cholinergic drugs on intraocular pressure after chemical sympathectomy produced by 6-hydroxydopamine has been examined in rabbits. For comparison, ocular tension in response to these same drugs has been measured after chronic treatment of rabbits with the norepinephrine synthesis inhibitor alpha-methyl-para-tyrosine. The results indicated that the effects of these 2 treatments were both qualitatively and quantitatively similar. In both cases, supersensitivity to the pressure-lowering effects of alpha and beta adrenergic amines developed. After administration of cholinergic drugs, however, ocular tension became elevated to values ranging from 3 to 7 mm Hg above the baseline levels.     

Comparison of two iron gluconate treatment modalities in chronic hemodialysis patients: results of a randomized trial

BACKGROUND: Iron supplementation in chronic hemodialyzed patients is not yet completely defined concerning the dosing regimen. This study aimed to evaluate the effects of the same iron load administered in different regimens on anemia, iron status and the reticulocyte (Ret) subpopulation patterns in stable patients on chronic hemodialysis (HD). Patients and methods: Seventeen patients undergoing thrice-weekly chronic HD and receiving stable alphaerythropoietin therapy with absolute iron deficiency (transferrin saturation (TSAT) <20%, ferritin (Frt) <100 ng/mL) were randomly divided into two groups: group A (n=9) received 20.8 mg of sodium iron gluconate at the end of each dialysis session; group B (n=8) 62.5 mg only at the end of the 1st dialysis session of the week. The treatment period lasted 3 months (period 1) and was followed by 3 months of observation (period 2). Results: Both treatments increased hemoglobin (Hb) levels by an average of 0.90 g/dL in period 1, with a progressive decline in period 2 (p=ns between groups), peaking at 11.2 g/dL in group A and 10.8 g/dL in group B. The effects on mean red blood cell volume and Hb concentrations were similar. Frt levels more than doubled during period 1 and early in period 2 in both groups (172 microg/L in group A; 149 microg/L in group B, and progressively decreased in period 2 (p=ns between groups). The TSAT index increased progressively peaking to 28.7% in group A and 24.3% in group B. Hypochromic red blood cells (hypocRBC) decreased early from 5.6-2.2% in group A, and from 5.5-2.1% in group B, and persisted in period 2; the between-period differences for the combined groups were statistically significant (p=0.0051). High fluorescence reticulocytes (HFR) increased from period 1 to period 2 only in group B (from 0.8-1.7%, p=0.012). CONCLUSIONS: Both regimens replenished iron stores and improved anemia. The HFR increase in group B could be due to soluble transferring receptor (STnfR) gene upregulation; alternatively it could indicate the prevalence of immature Ret release from bone marrow.