Regional anesthesia for carotid endarterectomy: a comparison between ropivacaine and levobupivacaine.

BACKGROUND: This study compares ropivacaine and levobupivacaine when administered for cervical plexus block. The authors therefore compared the arterial pressure profile and the incidence of hypotension between drugs. METHODS: Forty-eight patients scheduled for carotid artery surgery (American Society of Anesthesiologists [ASA] 2-3) were randomly assigned to receive levobupivacaine or ropivacaine (24 patients each). Neurological status, arterial pressure profile and control of postoperative pain were the main observed parameters. All patients had severe carotid stenosis (>80%) and/or had suffered transient ischemic attacks (TIAs) or preoperative strokes. The same team performed anesthesia and surgery for carotid endarterectomy; the cervical block was performed according to Moore's technique.Arterial pressure, heart rate and S(a)O(2p) were monitored continuously with particular regard to T0 (baseline), T1 (immediately before carotid clamping), T2 (immediately before declamping) and T3 (at the end of the procedure). Hypotension was defined as the fall of arterial systolic pressure 30% below baseline or less than 100 mmHg. RESULTS: Arterial pressure fell significantly in both groups at T1 with respect to T0 (P<0.0001). Levobupivacaine patients showed higher mean arterial pressure on T0 (112+/-12 mmHg versus 103+/-7 mmHg; P<0.05), thus suggesting a more pronounced vasodilator effect, as confirmed by the larger drop of arterial diastolic pressure (P=0.007). An absolute 6% difference of hypotension-related drug was recorded with levobupivacaine (19%) as compared with ropivacaine (13%) (P=0.28). CONCLUSIONS: Levobupivacaine has a greater vasodilatory effect than ropivacaine. Its higher incidence of hypotension, although not statistically significant, suggests ropivacaine as the drug of choice for cervical plexus block.

Glutamate signaling in chondrocytes and the potential involvement of NMDA receptors in cell proliferation and inflammatory gene expression.

OBJECTIVE: Increased levels of glutamate, the main excitatory neurotransmitter, are found in the synovial fluid of osteoarthritis (OA) patients. Our aim was to study glutamate signaling in chondrocytes, focusing on the composition, pharmacology, and functional role of N-methyl-d-aspartate (NMDA) glutamate receptors. METHODS: We used the human chondrocyte cell line SW1353 and, in parallel, primary rat articular chondrocytes. Glutamate release and uptake were measured by fluorimetric and radiometric methods, respectively. Gene expression was analyzed by quantitative polymerase chain reaction. NMDA receptor pharmacology was studied in binding experiments with [3H]MK-801, a specific NMDA receptor antagonist. RNA interference was used to knock-down the expression of NR1, a subunit of NMDA receptors. RESULTS: Glutamate release, sodium- and calcium-dependent glutamate uptake, and the expression of a glutamate transporter were observed in chondrocytes. NR2D was the most abundant NMDA receptor subunit in these cells. Consistent with this observation, the binding affinity of [3H]MK-801 was much lower in chondrocytes than in rat brain membranes (mean K(d) values of 700 and 2.6 nM, respectively). NR1 knock-down, as well as NMDA receptor blockade with MK-801, reduced chondrocyte proliferation. Interleukin (IL)-1beta significantly altered glutamate release and uptake (about 90% increase and 50% decrease, respectively, in SW1353 cells). Moreover, IL-1beta induced the gene expression of cytokines and enzymes involved in cartilage degradation, and MK-801 significantly inhibited this response. CONCLUSIONS: Our findings suggest that chondrocytes express a self-sufficient machinery for glutamate signaling, including a peripheral NMDA receptor with unique properties. This receptor may have a role in the inflammatory process associated with cartilage degradation, thus emerging as a potential pharmacological target in OA.

[Anticoagulation and chronic hemodialysis]. / Anticoagulazione ed emodialisi cronica.

The application of effective hemodialysis in humans was delayed until the development of cellulose-based membranes in 1940s, and the advent of heparin as the primary means of anticoagulation. Unfractionated heparin is still the most commonly used agent for anticoagulation, but its potentially serious complications, such as hemorrhage and heparin-induced thrombocytopenia type II, led the scientific community to consider other options to counteract coagulation. ''Low heparin dialysis'', ''heparin-free dialysis'', regional heparinization, low molecular weight heparins, citrate, prostacyclin, nafamostat, low molecular weight heparanoid and direct thrombin inhibitors are among these methods and have different safety, efficacy and cost. In general, hemodialysis patients with active hemorrhage or at high risk for bleeding complications are best treated with heparin-free hemodialysis. Low molecular weight heparanoid and direct thrombin inhibitors (recombinant hirudin or argatroban) may be useful for anticoagulation of the extracorporeal circuit in the rare patients with confirmed heparin-induced thrombocytopenia type II, who cannot be dialyzed with heparin.

Transmembrane pressure modulation in high-volume mixed hemodiafiltration to optimize efficiency and minimize protein loss.

The aim of the present study was transmembrane pressure (TMP) modulation in high-volume mixed hemodiafiltration (HDF) to optimize efficiency and minimize protein loss. The optimal flow/pressure conditions in on-line mixed HDF assisted with a feedback control of TMP were defined in this prospective randomized study in order to obtain maximal efficiency in solute removal while minimizing potential side effects. Two different TMP profiles in mixed HDF were compared in 12 unselected patients who underwent two study periods of 2 weeks each in cross-over randomized sequence: (A) constant TMP at around 300 mmHg and (B) profiled TMP, in which TMP was slowly increased from a low initial value to the maximal value. In both procedures, the mean volume exchange was 10.6+/-1.4 l/h. Mean filtration fraction was 53%. Instantaneous beta2-microglobulin (beta2-m) clearance was higher at the start of the session with profiled TMP (207+/-35 vs 194+/-28 ml/min, P<0.005), whereas no differences were found at the end (135+/-19 vs 132+/-19 ml/min). Profiled TMP resulted in a higher mean beta2-m clearance of the session (97.0+/-15.4 vs 87.8+/-18.3 ml/min, P<0.01), in lower albumin loss in the first 30 min (0.62+/-0.14 vs 0.98+/-0.18 g, P<0.0001), and, in the whole session (3.98+/-1.19 vs 5.24+/-0.77 g, P<0.001), in higher dialyzer ultrafiltration coefficients and lower resistance indexes. This study showed that the TMP feedback modulation in mixed HDF was highly effective in maintaining very high ultrafiltration rates and filtration fractions, and minimized potential side effects as a result of the improved preservation of membrane permeability and more favorable dialyzer pressure regimen.

Kaposi's sarcoma in a patient with focal glomerulosclerosis.

We report the clinical features and outcome af a patient who presented Kaposi's sarcoma following immunosuppressive therapy for FGS; Cyclophosphamide and steroids were administered; the patient recovered after three months treatment with i.v. vinblastine.

Distal arteriovenous fistulas in elderly hemodialysis patients.

Dialysis access procedures and complications are an important cause of morbidity and hospitalization for chronic hemodialysis patients. Subjects over 65 years old have a higher incidence of co-morbid factors (diabetes mellitus, atheros clerosis, neoplasms, heart failure), therefore the correct choice in terms of timing and type of permanent access is extremely important. As elbow fistulas are often complicated by heart failure and PTFE grafts have a higher risk of thrombosis, we decided to evaluate the success rate of distal fistula as primary dialysis access in elderly patients. We carried out a retrospective study to identify survival predictors and actual vascular network saving. Between January 1991 and September 2000, 277 vascular access procedures were performed on 198 elderly patients (age 65 or older). The first anastomosis was positioned as peripherally as possible. In cases of patients with poor peripheral vasculature or three co-morbid factors, vascular access was first created at the origin of radial artery (Toledo-Pereyra fistula). Survival (Kaplan - Meyer analysis) was significantly higher for Toledo-Pereyra fistulas compared to wrist and snuff-box ones, in spite of the presence of a high incidence of co-morbid factors. We conclude that Toledo-Pereyra fistula is an efficient primary choice in elderly patients.

Erythrocyte voltage-dependent calcium influx is reduced in hemodialyzed patients.

BACKGROUND: Uremia displays increased cytosolic free calcium ([Ca2+]i) in many different cell types, supporting the hypothesis of an altered Ca2+ transport modifying the functional activity of calcium signaling pathway. METHODS: Thirty-five hemodialyzed patients and 20 age-matched subjects were studied. Erythrocyte resting [Ca2+]i and Ca2+ influx were measured by the fluorescent Ca2+-sensitive dye fura-2. RESULTS: We found an increase of resting [Ca2+]i in erythrocytes from uremic hemodialyzed patients compared with matched healthy controls (103 +/- 2.5 nM, N = 20, vs. 90 +/- 4, N = 20, P < 0.01). Moreover, we found an altered voltage-dependent Ca2+ influx showing a reduced transport rate (0.42 +/- 0.03 nM/second vs. 0.74 +/- 0.08, P < 0.01). High levels of plasma parathyroid hormone (PTH) were related to augmented Ca2+ entry (r = 0.511, P < 0.05), contributing to maintain a high level of [Ca2+]i. Hemodialysis had no effect on cell calcium level and Ca2+ influx indices. The therapy with Ca2+ antagonists did not modify the values of resting [Ca2+]i or Ca2+ influx indices, but the correlation between PTH and influx indices was lost. CONCLUSIONS: In conclusion, we found evidence for an alteration of erythrocyte Ca2+ influx caused by uremic toxicity that could be related to some organ disorders in uremia. The chronic increase of cellular calcium may contribute to influx derangement.

Study of calcium metabolism in idiopathic hypercalciuria by strontium oral load test.

Calcium excretion and absorption were evaluated in hypercalciuric calcium stone formers by the study of Sr2+ excretion and absorption after an oral load. Ca2+ stone formers (n = 140) were studied, and the results were compared in the 83 of them who had idiopathic hypercalciuria and in the 57 who had Ca2+ excretion within reference values. Hypercalciuric patients showed increased renal Sr2+ clearance (CRE; 5.26 +/- 0.358 vs 3.29 +/- 0.277 mL/min; P <0.001), whereas Sr2+ absorption [assessed as the area under the serum concentration-time curve (AUC)] was increased at 30 and 60 min (1.53 +/- 0.087 vs 1.21 +/- 0.071 mmol. L-1. min; P <0.05), but not at 240 min after the load. In hypercalciuric patients, the AUCs were positively correlated with urinary Sr2+ fractional excretion (P <0. 001). Conversely, in normocalciuric patients plasma parathyroid hormone (PTH) was negatively correlated with the AUCs (P <0.01) and CRE (P <0.05), whereas 1,25-dihydroxyvitamin D plasma concentrations normalized to PTH were positively correlated with the AUCs (P <0.05). The results of Sr2+ load tests suggest that in the hypercalciuric population, Ca2+ absorption is altered predominantly in the duodenum and that the normal regulation exerted by calciotropic hormones on tubular and enteral Ca2+ handling is lost.

Strontium absorption and excretion in normocalciuric subjects: relation to calcium metabolism.

The relationships of Sr intestinal absorption and renal excretion with biohumoral factors regulating Ca metabolism were studied in 47 normocalciuric subjects with Ca kidney stones. Sr concentrations were measured in serum and urine after an oral load of stable Sr (30.2 mumol/kg body wt). Enteral absorption of the ion (9.77 +/- 0.438 mmol.L-1.min, 240 min after Sr administration), expressed as the area under the plasma concentration-time curve (AUC), and renal clearance (CRE) in these subjects during the test (2.80 +/- 0.336 mL/min) were not different from values for 27 controls. CRE was not correlated with AUCs. Plasma concentrations of parathyroid hormone (PTH) negatively correlated with AUCs (P < 0.01) and correlated with CRE after one outlier was excluded (P < 0.05). Plasma concentrations of 1,25-dihydroxyvitamin D correlated positively with AUCs (P < 0.01) when normalized to the plasma concentration of PTH. Multiple stepwise regression showed that PTH and phosphatemia were significantly related to AUC values at 240 min (P < 0.01). These findings suggest that Sr absorption and excretion reflect the regulation of Ca metabolism, but some differences in renal handling of the two ions may exist.

Characterization of voltage-dependent calcium influx in human erythrocytes by fura-2.

Thus far, the methods used to determine erythrocyte Ca2+ influx have not allowed the assessment of the kinetics of ion uptake. To overcome this drawback, we studied a new method, using the fluorescent Ca2+-chelator fura-2, which directly quantifies intracellular Ca2+ changes in human erythrocytes. This method has the advantage over previous techniques that it monitors continuously cellular Ca2+ levels. The Ca2+ influx is modulated by cellular membrane potential in the presence of a transmembrane Ca2+ concentration gradient and exhibits a first slow increase of the intracellular Ca2+ concentration, followed, after the reachment of a threshold value of 125 +/- 13 nM Ca2+, by a faster increase until a plateau is reached. The influx rate is inhibited by dihydropyridines in the micromolar range. These findings support the hypothesis that erythrocyte Ca2+ influx is mediated by a carrier similar to the slow Ca2+ channels and is dependent on membrane depolarization.

Nonacidotic proximal tubulopathy transmitted as autosomal dominant trait.

The family of a patient with a nonacidotic and hypercalciuric proximal tubulopathy was studied. The proband showed glycosuria, aminoaciduria, tubular proteinuria, renal hypophosphatemia, and urate tubular hyporeabsorption without bicarbonate loss. He also presented increased urine calcium excretion, plasma 1,25-dihydroxyvitamin D, and enteral calcium absorption. Clinical consequences of the tubulopathy were osteopenia and calcium kidney stones. Fifteen of the proband's relatives were studied; six of them had renal hypophosphatemia, 10 presented hypercalciuria, and three showed both hypercalciuria and hypophosphatemia. No other reabsorption defects were observed. High plasma levels of 1,25-dihydroxyvitamin D were found in 13 family members; their values correlated positively with calcium excretion and negatively with tubular phosphate reabsorption. None produced stones or had reduced mineral bone density. Hypophosphatemia and hypercalciuria occurred in the two generations studied; their transmission was independent of gender, and male-to-male transmission occurred for both defects. Our findings suggest that a genetic alteration of proximal tubular function could cause multiple reabsorption defects in the proband or renal phosphate leakage in the proband's relatives. The genotypic alteration causing the proximal dysfunctions may be monogenic, with an autosomal dominant pattern of inheritance and variable expressivity. Increased calcium excretion may be due to the proximal tubular alteration; alternatively, it may be the result of a genetic background predisposing to idiopathic hypercalciuria. Phosphate and calcium loss could stimulate 1,25-dihydroxyvitamin D synthesis in proximal tubular cells.

(Ca+Mg)ATPase and calcium influx in erythrocytes of patients with idiopathic hypercalciuria.

Increased erythrocyte (Ca+Mg)ATPase activity was previously observed in idiopathic hypercalciuria. In order to verify if this alteration is a primary or a secondary event, we studied Sr influx in erythrocytes from subjects with idiopathic hypercalciuria. (Ca+Mg)ATPase activity was significantly higher in hypercalciuric than in hypercalciuric than in normocalciuric subjects whereas no difference in Sr influx was found between the two groups. (Ca+Mg)ATPase activity positively correlated with the erythrocyte Sr content found after 5 min of incubation and with urine Ca excretion. The normal Sr permeability suggests that (Ca+Mg)ATPase is primarily altered in idiopathic hypercalciuria. The primary increase of (Ca+Mg)ATPase activity may enhance passive Ca influx by reduction of cellular Ca concentration. It may induce a defect in cellular Ca metabolism that may cause idiopathic hypercalciuria by stimulating bone Ca turn-over and enteral Ca absorption.